Pure red cell aplasia (PRCA) is characterized by isolated anemia and a marked reduction or absence of erythroid precursors in the bone marrow. Depending on the underlying etiology, treatment may include immunomodulation or cytotoxic agents, chronic red blood cell transfusions, or hematopoietic stem cell transplantation. Parvovirus B19 infection is a well-recognized cause of transient PRCA, typically resolving with viral clearance. We report an unusual late relapse of PRCA occurring years after parvovirus B19 eradication, unresponsive to steroids and mycophenolate mofetil. Remarkably, prolonged treatment with intravenous immune globulin (IVIG) resulted in complete remission, highlighting its therapeutic utility for idiopathic PRCA.

Climate change is leading to more frequent and severe extreme temperature events, negatively impacting agricultural productivity and threatening global food security. Plant reproduction, the process underpinning crop yield, is highly susceptible to heatwaves, affecting pollen development and ultimately affecting seed set and crop yields. Recent research has increasingly focused on understanding how pollen grains from various crops react to heat stress at the molecular and cellular levels. This surge in interest over the last decade has been underpinned by advances in genomic technologies, such as single-cell RNA sequencing, which holds significant potential for revealing the underlying regulatory reprogramming triggered by heat stress throughout the various stages of pollen development. This review focuses on how heat stress affects gene regulatory networks, including the heat stress response, the unfolded protein response, and autophagy, and discusses the impact of these changes on various stages of pollen development. It highlights the potential of pollen selection as a key strategy for improving heat tolerance in crops by leveraging the genetic variability among pollen grains. Additionally, genome-wide association studies and population screenings have shed light on the genetic underpinnings of traits in major crops that respond to high temperatures during male reproductive stages. Moreover, gene-editing tools like CRISPR/Cas systems could facilitate precise genetic modifications to boost pollen heat resilience. The information covered in this review is valuable for selecting traits and employing molecular genetic approaches to develop heat-tolerant genotypes.

Introduction:Invasive cribriform carcinoma of the breast, initially described by Page et al in 1983 due to its predominant cribriform growth pattern in the invasive component and relatively favourable prognosis, is a rare type of breast carcinoma, accounting for 0.3 to 3.5% of primary breast carcinomas [1, 2]. ICC patients typically have a small tumour size, few axillary lymph node invasion, low distant metastasis rate, tumour with a high frequency of well differentiation, high ER and PR positive rates with rarely-observed human epidermal growth factor receptor 2 (HER2) amplification and a low proliferation index [3, 4, 5]. To date, studies of skin manifestations of invasive cribriform breast of the breast are notably scarce. We herein report a patient of ICC with a presentation as an erythematous papule on the nipple that no one has reported before.Case history / examination:A 71-year-old Asian woman visited our Department of Dermatology with a chief complaint of a reddish protruding skin lesion on the tip of her right nipple that had appeared for 6 months. Upon physical examination, the skin lesion was a solitary, well-demarcated papule, 0.2 by 0.2 cm in size, appearing centrally erythematous with violaceous in the periphery, fairly dome-shaped and firm [Figure 1a-c]. Besides, the papule was completely asymptomatic. The patient did not report any other abnormal symptoms. Her medical history was also unremarkable.Differential diagnosis and investigations:With these clues, a benign skin lesion had been impressed. Therefore, a local excision was performed to obtain a specimen of 0.7 by 0.5 by 0.3 cm in size. Biopsy results turned out to be pure invasive cribriform carcinoma of the breast (pure ICC), characterized by the invasive cribriform pattern comprising >90% of the lesion, in addition to mammary Paget’s disease (MPD) in the epidermis [Figure 2a-c]. Immunohistochemical tests showed positive expressions of both oestrogen and progesterone receptors [ER >95%, PgR >95%]. The reaction to HER2 (human epidermal growth factor receptor type 2) protein was negative [HER 2 (-)] [Figure 3a-c]. The Ki-67 labelling index was 5 %.Treatment, outcome and follow-up:In the diagnosis of pure ICC with MPD, she was referred to the Breast Surgery Department for further survey and treatment. Results on both CEA and CA15-3 levels were normal. Bilateral breast mammography (CC and MLO view) revealed segmental fine pleomorphic microcalcifications in the lower-inner quadrant of her right breast. These findings raise high suspicion for malignancy and are consistent with a classification of 4C in the BIRADS-US system. Breast ultrasound revealed two oval hypoechoic lesions with tiny calcifications which were 7.8 mm and 24.5 mm in size at the right breast near the areola. Whole body bone scan found no evidence of bone metastasis. With a previous biopsy pathology report revealing ICC and MPD, a full discussion was carried out with the patient. Finally, a simple mastectomy and sentinel lymph node biopsy were performed on her right breast.With the right side simple mastectomy, pathology of the surgical specimen showed residual multifocal ductal carcinomas in situ. Both frozen sections of sentinel lymph nodes revealed no evidence of metastasis. The pathological TNM stage was pT1aN0 according to AJCC eighth edition. Further treatment plans for this patient included a five-year Tamoxifen therapy and regular follow-up at the Breast Surgery Department.Discussion:Based on the clinical features of the papule on her nipple, our initial impressions were benign skin lesions such as pyogenic granuloma, nipple adenoma, Spitz nevus and intradermal nevus. However, the pathologic diagnosis was pure ICC with MPD in the epidermis. Although ICC usually presents as an asymptomatic mass or may even be clinically occult[1, 3], the chance of ICC presenting as skin lesions cannot be ignored. The case reported by Katarzyna et al, in which ICC mimicked a breast abscess [6], along with our case of ICC presenting as a nipple papule, collectively demonstrates ICC’s potential to primarily manifest through skin lesions. To the best of our knowledge, ICC is a tumour having a more favourable prognosis than invasive breast carcinoma with less cribriform pattern and low grade invasive ductal carcinoma [11]. Despite favourable prognosis of ICC, there are still chances of aggressive behaviour or development into an advanced stage if left untreated long enough. Mishra et al reported a case of ICC with extensive perineural infiltration and lymphovascular invasion in a 58-year-old female; and Zhang et al also reported a case of pure ICC with bone metastasis when left untreated for 13 years[7, 8]. Therefore, such manifestation of a papule on the nipple, as in our case, may result in delayed diagnosis and treatment to ICC. It is crucial for dermatologists to have early awareness about skin manifestation of ICC and to avoid misdiagnosis.Mammary Paget’s disease (MPD), first described by Sir Paget in 1874 as eczematous nipple and areola skin lesions, is a rare form of breast carcinoma comprising 1 to 3% of all breast cancers. Nearly all cases of MPD are affiliated with underlying breast carcinomas, typically located near the areola, and >90% are either ductal carcinomas in situ (DCIS) or invasive ductal carcinomas (IDC). Pathophysiologically, there are two main hypotheses proposed for the origin of MPD: the epidermotropic theory and the malignant transformation theory. The epidermotropic theory states that Paget cells originate from underlying breast carcinoma, and they migrate via the lactiferous ducts to the epidermis of the nipple. On the other hand, the malignant transformation theory states that Paget cells are malignant transformation of pluripotent keratinocyte stem cells or cells of apocrine gland ducts[9]. Although remains controversial, it is currently widely accepted that MPD is associated with underlying breast carcinoma, forming the concept based on the epidermotropic theory. In our case, ICC and MPD were diagnosed within the papular lesion on the nipple. This case stands out from >90% of cases in which mammary Paget’s disease was diagnosed exclusively with underlying DCIS or IDC. Furthermore, to the best of knowledge, only one publication focusing on radiologic characteristics of 52 MPD cases mentioned a case of invasive lobular and invasive cribriform carcinoma being diagnosed with mammary Paget’s disease presenting as a mass on mammography[10], but details or images were not provided. As to our case, it is worth knowing that the patient was diagnosed with multifocal DCIS at 1 cm near the right areola in the surgical specimen from simple mastectomy. In our opinion, it was the invasive cribriform carcinoma of the breast but not DCIS resulting in the mammary Paget’s disease in the epidermis of the papule [Figure 2c] as consistent with the epidermotropic theory. Although DCIS has been diagnosed near the areola, we believe that the chance of mammary Paget’s disease originating from the DCIS was slim. That is because malignant Paget cells were not seen at other parts of the nipple nor at the areola, but merely in the epidermis of the papule on the nipple. Furthermore, based on pathologic images, the gross pictures and the clinical manifestations of ICC and MPD, we believe that the invasive cribriform carcinoma of breast had caused the dome-shaped violaceous papule on the nipple, and mammary Paget’s disease contributed to the central erythematous part of the papular lesion [Figure 1a]. Undoubtedly, more studies are needed to bring attention to the skin manifestation of invasive cribriform carcinoma of the breast. As far as we know, no publication has ever reported on ICC with skin manifestation as a papule on the nipple. Also, no case has been reported with detailed images and descriptions regarding a pure ICC being diagnosed with MPD. In this case report, we aim to bring awareness to skin manifestation of ICC.References:1. Cong Y, Qiao G, Zou H, Lin J, Wang X, Li X, et al. Invasive cribriform carcinoma of the breast: A report of nine cases and a review of the literature. Oncol Lett. 2015;9: 1753-1758.2. Page DL, Dixon JM, Anderson TJ, Lee D, Stewart HJ. Invasive cribriform carcinoma of the breast. Histopathology. 1983;7: 525-36.3. Zhang W, Zhang T, Lin Z, Zhang X, Liu F, Wang Y, et al. Invasive cribriform carcinoma in a Chinese population: comparison with low-grade invasive ductal carcinoma-not otherwise specified. Int J Clin Exp Pathol. 2013;6: 445-57.4. Mo CH, Ackbarkhan Z, Gu YY, Chen G, Pang YY, Dang YW, et al. Invasive cribriform carcinoma of the breast: a clinicopathological analysis of 12 cases with review of literature. Int J Clin Exp Pathol. 2017;10: 9917-9924.5. Liu J, Zheng X, Han Z, Lin S, Han H, Xu C. Clinical characteristics and overall survival prognostic nomogram for invasive cribriform carcinoma of breast: a SEER population-based analysis. BMC Cancer. 2021;21: 168.6. Dobruch-Sobczak K, Roszkowska-Purska K, Chrapowicki E. Cribriform carcinoma mimicking breast abscess - case report. Diagnostic and therapeutic management. J Ultrason. 2013;13: 222-9.7. Zhang W, Lin Z, Zhang T, Liu F, Niu Y. A pure invasive cribriform carcinoma of the breast with bone metastasis if untreated for thirteen years: a case report and literature review. World J Surg Oncol. 2012;10: 251.8. Mishra S, Yadav K, Singh Anshul, Misra Vatsala, Chaudhary Kuldeep. Unusual case of Invasive Cribriform Carcinoma of Breast (ICC). JCR [serial online] 20219. Lopes Filho LL, Lopes IM, Lopes LR, Enokihara MM, Michalany AO, Matsunaga N. Mammary and extramammary Paget’s disease. An Bras Dermatol. 2015;90: 225-31.10. Günhan-Bilgen I, Oktay A. Paget’s disease of the breast: clinical, mammographic, sonographic and pathologic findings in 52 cases. Eur J Radiol. 2006;60: 256-63.

Purpose: This study aims to investigate the potential causal relationship between the use of indapamide and rhabdomyolysis. Previous research and pharmacovigilance monitoring activities have suggested a potential association between indapamide use and rhabdomyolysis. However, limited information is available on this association. Methods: A case-control study conducted using EHR data, between July 1,2016, and December 31,2022. Patients who have rhabdomyolysis event (cases) were matched to four controls bases on age, gender and date. We examined the odds for indapamide exposure through three risk periods: current use, recent use, and former. The study outcome was ascertained through the presence of CK level over 1,000 U/L (i.e. rhabdomyolysis event). Subsequently, a multivariable conditional logistic regression analysis was utilized to assess the causal impact of indapamide exposure on the likelihood of developing rhabdomyolysis, while accounting for potential confounding variables. Results: The study population consisted of 2,965 cases and 11,860 controls. The results of the conditional logistic regression analysis indicated a lack of association between exposure to indapamide for the current users the OR was 0.7 (95% CI: 0.49 - 0.92) and the AOR was 0.6 (95% CI: 0.39 - 1.05). The recent users showed OR of 0.9 (95% CI: 0.56 - 1.50) and AOR of 0.2 (95% CI: 0.14 - 0.47). Lastly, the former users demonstrated an OR of 0.8 (95% CI: 0.47 - 1.26), and AOR of 0.1 (95% CI: 0.07 - 0.23). Conclusions: In this study, we did not find association between indapamide use and rhabdomyolysis regardless timing of exposure.

Globally, obstetric fistula is a tragic outcome following obstructed labor. Failure of complex repairs and post-operative incontinence are common. We describe an innovative surgical technique incorporating the rectus abdominis muscle flap at the time of fistula repair. We report outcomes from six patients at the Fistula Care Center in Lilongwe, Malawi in October 2023. At three months following discharge, five patients (80.0%) were continent; one patient was unable to follow-up but was continent at a one-month phone follow-up. There were no major complications. The rectus abdominis muscle flap may be considered in challenging obstetric fistula repairs.

Modulating lattice strain in intermetallic compounds could effectively alter their electronic structure and binding energy, thus impacting catalytic activity. Strain is usually induced through lattice mismatch, achieved by constructing core-shell nanostructures or metal-substrate interfaces with complex reciprocity and distractors. However, in situ induced strain without interface-construction or lattice mismatch presents challenges. In this study, we precisely manipulate consecutive compressive strain from -0.5% to -0.8% in CoPt 3Pd intermetallic compound by inducing interior atomic radius mismatch. Precise strain control results in a negative shift of d-band center, dynamic charge distribution, and facilitates water dissociation, leading to the enhanced electrocatalytic activity. The CoPt 3Pd catalyst with -0.5% compressive strain exhibits exceptional hydrogen evolution activity, with an overpotential of 169 mV at 1 A cm -2. Our approach offers a straightforward method to manipulate compressive strain on intermetallic compound by atomic size mismatch, with broad implications for catalytic processes.

The uniform exponential stabilities (UESs) of two hybrid control systems comprised of a wave equation and a second-order ordinary differential equation are investigated in this study. Linear feedback law and local viscosity are considered, as are nonlinear feedback law and internal anti-damping. The hybrid system is first reduced to a first order port-Hamiltonian system with dynamical boundary conditions, and the resulting system is discretized using the average central-difference scheme. Second, the UES of the discrete system is obtained without prior knowledge of the exponential stability of the continuous system. The frequency domain characterization of UES for a family of contractive semigroups and the discrete multiplier approach are used to validate the main conclusions. Finally, the Trotter-Kato Theorem is used to perform a convergence study on the numerical approximation approach. Most notably, the exponential stability of the continuous system is derived by the convergence of energy and UES, which is a novel approach to studying the exponential stability of some complex systems. Numerical simulation is used to validate the effectiveness of the numerical approximating strategy.

The neurovisceral integration model proposes that information flows bidirectionally between the brain and the heart via the vagus nerves and vagally-mediated heart rate variability (vmHRV) can be used to index heart-brain interaction. Recent research has shown that voluntary reduction of breathing rate (slow-paced breathing, SPB) can enhance cardiac vagal control. Additionally, prefrontal transcranial direct current stimulation (tDCS) can modulate the excitability of the prefrontal region and influence the vagus nerve. However, fundamental research on the combination of SPB and prefrontal tDCS to increase vmHRV and other physiological indices of the autonomic nervous system is scarce. Therefore, 200 healthy participants were assigned to four experimental groups. Each group received either 20 min of active or sham tDCS combined with 5.5 breath per minute (BPM) or 15 BPM breathing. Regardless of the tDCS condition, the SPB group showed a significant increase in vmHRV over 20 minutes, suggesting an increase in parasympathetic activity. In addition, a significant decrease in HR at the first and second 5-minute epochs of the intervention. Regardless of breathing condition, the active tDCS group exhibited higher HR at the fourth 5-minute epoch of the intervention compared to the sham tDCS group, suggesting more sympathetic arousal. However, there was no combined effect on vmHRV, HR, skin conductance, or blood pressure. SPB is a robust technique for increasing vmHRV, whereas prefrontal tDCS may produce effects that counteract those of SPB. More research is necessary to test whether and how top-down and bottom-up approaches can be combined to improve vagal control.

Hemangioblastomas are the most common tumor associated with Von Hippel-Lindau (VHL) and a leading cause of mortality. We present five pediatric patients with VHL-associated hemangioblastomas treated with belzutifan, a HIF2a inhibitor. Three patients were started on belzutifan due to vision loss from progressive retinal hemangioblastomas. Within 1 year of treatment, all three patients had improvement in hemangioblastoma size and visual acuity. For patients with intracranial lesions, belzutifan resulted in an improvement in neurologic symptoms and hemangioblastoma size. Four patients experienced grade 1-2 anemia and two patients required a dose reduction. Our report suggests that belzutifan can be an effective therapy for pediatric patients with VHL-associated hemangioblastomas.

ABSTRACT.Squamous cell carcinoma (SCC) of the bladder is a rare urologic malignancy, estimated to affect 3% to 5% of the bladder. Squamous cell carcinoma (SCC) of the bladder remains the most common subtype throughout Africa. Most literatures focused on management of Transitional cell carcinoma(TCC) with fewer discussion in SCC management. TCC typically presents with painless hematuria, whereas SCC presents with painful hematuria, bladder mass, and necroturia. SCC is mostly radioresistant and does not respond to chemotherapy. The mainstay treatment is Partial Cystectomy or radical cystectomy, which can be performed through open surgery, laparoscopic or robot-assisted approach, all techniques with acceptable results. We report a case with favourable outcome following partial cystectomy which was managed by open surgery. In a 12months follow up the patient remained asymptomatic with good surgical outcome.

This paper focuses on the existence of normalized solutions for the Chern-Simons-Schrödinger system with mixed dispersion and critical exponential growth. These solutions correspond to critical points of the underlying energy functional under the L 2 -norm constraint, namely, ∫ R 2 u 2 d x = c > 0 . Under certain mild assumptions, we establish the existence of nontrivial solutions by developing new mathematical strategies and analytical techniques for the given system. These results extend and improve the results in the existing literature.

A document by Lingyu Fu. Click on the document to view its contents.

Genetic analyses of host-specific parasites can elucidate the evolutionary histories and biological features of their hosts. Here, we used population-genomic analyses of ectoparasitic seal lice (Echinophthirius horridus) to shed light on the postglacial history of seals in the Arctic Ocean and the Baltic Sea region. One key question was the enigmatic origin of relict landlocked ringed seal populations in lakes Saimaa and Ladoga in northern Europe. We found that that lice of four postglacially diverged subspecies of the ringed seal (Pusa hispida) and Baltic gray seal (Halichoerus grypus), like their hosts, form genetically differentiated entities. Using coalescent-based demographic inference, we show that the sequence of divergences of the louse populations is consistent with the geological history of lake formation. In addition, local effective population sizes of the lice are generally proportional to the census sizes of their respective seal host populations. Genome-based reconstructions of long-term effective population sizes revealed clear differences among louse populations associated with gray vs. ringed seals, with apparent links to Pleistocene and Holocene climatic variation as well as to the isolation histories of ringed seal subspecies. Interestingly, our analyses also revealed ancient gene flow between the lice of Baltic gray and ringed seals, suggesting that the distributions of Baltic seals overlapped to a greater extent in the past than is the case today. Taken together, our results demonstrate how genomic information from specialized parasites with higher mutation and substitution rates than their hosts can potentially illuminate finer scale population genetic patterns than similar data from their hosts.

Protein cis-regulatory elements (CREs) are regions that modulate the activity of a protein through intramolecular interactions. Kinases, pivotal enzymes in numerous biological processes, often undergo regulatory control via inhibitory interactions in cis. This study delves into the mechanisms of cis regulation in kinases mediated by CREs, employing a combined structural and sequence analysis. To accomplish this, we curated an extensive dataset of kinases featuring annotated CREs, organized into homolog families through multiple sequence alignments. Key molecular attributes, including disorder and secondary structure content, active and ATP-binding sites, post-translational modifications, and disease-associated mutations, were systematically mapped onto all sequences. Additionally, we explored the potential for conformational changes between active and inactive states. Finally, we explored the presence of these kinases within membraneless organelles and elucidated their functional roles therein. CREs display a continuum of structures, ranging from short disordered stretches to fully folded domains. The adaptability demonstrated by CREs in achieving the common goal of kinase inhibition spans from direct autoinhibitory interaction with the active site within the kinase domain, to CREs binding to an alternative site, inducing allosteric regulation revealing distinct types of inhibitory mechanisms, which we exemplify by archetypical representative systems. While this study provides a systematic approach to comprehend kinase CREs, further experimental investigations are imperative to unravel the complexity within distinct kinase families. The insights gleaned from this research lay the foundation for future studies aiming to decipher the molecular basis of kinase dysregulation, and explore potential therapeutic interventions.

The RETERO project develops new methods to Reduce, Replace and Refine (3R-principle) animal experiments for assessing the risk of harm to fish when passing through turbines or pumps. Since behavior of fish influences the mortality risk during turbine and pump passages, knowledge about species-specific behavior and its triggers are necessary. A primary objective of the RETERO project is the study of fish behavior in hydraulic conditions similar to turbine and pump intakes. Therefore, an experimental conduit was constructed at the Hubert-Engels Laboratory of Technische Universität Dresden (Germany) specifically for the RETERO project’s study on fish behavior, equipped with a 3D camera infrared tracking system. The conduit was designed to model hydraulic conditions typical for turbine and pump intakes. In the experimental setup the effects of flow velocities exceeding the maximum swim speed of fish, as well as spatial velocity gradients and illumination conditions, on the fish behavior are studied. The data from studies involving brown trout ( Salmo trutta) allow for an analysis of how these fish react to flow accelerations and velocities surpassing their sprint speed, using quantitative metrics for movement and activity. An initial evaluation of these experiments highlights the potential of this approach for further research.

Amyloidosis are a group of diseases in which soluble proteins aggregate and deposit in fibrillar conformation extracellularly in tissues. The effectiveness of therapeutic strategies depends on the specific protein involved, being crucial to accurately determine its nature. Moreover, following the diagnosis, the search for the mutation within relatives allows the clinical advice. Here we report the precise diagnosis and explored the possible reasons of the structural pathogenicity. Whole exome sequencing and GATK calling pipeline were leveraged to characterize the protein variant present in a patient with kidney failure. Bioinformatics strategies were applied to suggest potential explanations of the variants aggregation. Our pipeline allowed the identification of a single point variant of fibrinogen Aα chain, which opened the possibility of curative transplantation. I n silico structural analysis, suggested that the pathogenicity of the variant may be attributed to a heightened susceptibility to yield a peptide prone to deposit as an oligomer with a β-sheet structure. Exploiting the comprehensive coverage of whole genome sequencing we managed to fill a vacant stage in the diagnosis of hereditary amyloidosis and to stimulate the advancement in biomedicine.

Background and Purpose: Fibroblast Growth Factor (FGF), VEGFR2, and CSF1R signalling pathways play a key role in the pathogenesis of multiple sclerosis (MS). Selective inhibition of FGFR by infigratinib in MOG35-55-induced EAE prevented severe first clinical episodes by 40%; inflammation and neurodegeneration were reduced, and remyelination was enhanced. Multi-kinase inhibition of FGFR1-3, CSF1R and VEGFR2 by AZD4547 may be more efficient in reducing inflammation, neurodegeneration and regeneration in the disease model. Experimental Approach: Female C57BL/6J mice were treated with AZD4547 (6.25 mg kg-1 or 12.5 mg kg-1) orally or placebo over 10 days either from time of EAE induction (prevention experiment) or onset of symptoms (suppression experiment). Effects on inflammation, neurodegeneration and remyelination were assessed at the peak of the disease (day 18/20 p.i.) and the chronic phase of EAE (day 41/42 p.i.). Key Results: In the prevention experiment, treatment with AZD4547 prevented severe first clinical episodes by 66.7 or 84.6% respectively. Mice treated with 12.5 mg kg-1 of AZD4547 hardly showed any symptoms in the chronic phase of EAE. In the suppression experiment, treatment with AZD4547 resulted in a long-lasting reduction of severe symptoms by 91 or 100%. Inflammation and demyelination were reduced, and axonal density, numbers of oligodendrocytes and their precursor cells, and remyelinated axons were increased in both experimental approaches. Conclusion and Implications: Multi-kinase inhibition by AZD4547 in a well-tolerated dose of 1 mg kg-1 in humans may be a promising approach to reduce inflammation and neurodegeneration, to slow down disease progression and support remyelination in patients.

Issues surrounding gender equality are – and should be - front and centre in the water resources community, and other STEM fields. Very necessarily, the focus tends to remain on recruitment and inclusivity offering support for students and early career academics. The leaky pipeline concept used to describe the incremental loss of women from STEM fields with career duration results in a disproportionate loss of women, creating a parallel problem where highly qualified, top tier academics are disproportionately lost from the system after significant financial and personnel investment by institutions is made. Ultimately, the leaky pipeline undermines the extensive investment of the hydrology and other STEM communities in equity, diversity, inclusion, and accessibility (EDIA) recruitment and retention programs by cutting short career ambitions and the trajectories of diverse top performing individuals, resulting in no net benefit of EDIA policy investments. Addressing this critical gender gap requires the attention and support of the hydrology community of practice with specific focus on generating opportunities for advancement, confronting systemic and structural biases, and improving education around allyship. Institutions and professional organizations need to consciously grow diversity in leadership and recognize and outwardly manage the perception of academic excellence around slow research and education that attracts increased diversity. Supporting allyship, reducing competitiveness among community members, and reinforcing collaboration will not only attract, but retain, a higher proportion of diversity in the hydrology community, academia, and STEM professions in general. It is time for the water resources (and other STEM) communities to demand broader accountability and recognition of the barriers to women, implement and reward more diverse definitions of research excellence, and offer allyship training to the community of practice at large.