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The present investigation was undertaken to find out efficient strains of arbuscular mycorrhiza (AM fungi) alone or in combinations with Trichoderma viride for inoculation Dendrocalamus strictus L. seedlings. The inoculated seedlings showed good response having higher plant height, phosphorous ions content in root and shoot, AM spore number and root colonization than non-inoculated (control) seedlings in both single (alone) and co-inoculation (combined consortium) experiments. T. viride showed significant growth followed by Glomus mosseae, G. fasciculatum and mixed AM with single inoculation. In co-inoculation, the best growth responses were observed with G. fasciculatum + T. viride followed by G. mosseae + T. viride, mixed vesicular arbuscular mycorrhizas (VAM) + T. viride, G. mosseae + G. fasciculatum + T. viride + mixed VAM, G. mosseae + G. fasciculatum + T. viride and G. mosseae + G. fasciculatum after 120 days and also depicted maximum increase in phosphorus content of shoot and root when compared with other inoculated seedlings. However, all the inoculated seedlings showed significant increase in phosphorus content when compared with control seedlings.

The diversity of arbuscular mycorrhizal (AM) fungi of Acacia catechu Willd. was studied. Dominant AM spores, the bacterium Rhizobium sp. along with the fungus Trichoderma viride were isolated from the rhizosphere of A. catechu and mass-produced in laboratory. The co-inoculation effect of Glomus mosseae, Glomus fasciculatum, mixed AM (Glomus spp. [except G. mosseae, G. fasciculatum] with Acaulospora spp., Sclerocystis spp. and Gigaspora spp.), Rhizobium sp. and Trichoderma viride was studied as exerted on the growth of A. catechu seedlings. All inoculated seedlings showed improved seedling growth compared to the control. Inoculated seedlings had a pronounced effect on all growth parameters such as height, fresh and dry weight of roots and shoots, AM spore count, per cent mycorrhizal colonization in roots and root nodule number in comparison with uninoculated seedlings. Phosphorus uptake was also higher in inoculated seedlings than in the control. This study provides a good scope for commercially utilizing the efficient strains of AM fungi for beneficial effects with other beneficial rhizosphere microflora in the primary establishment of slow growing seedlings ensuring better survival and improved growth.

Endometriosis is often diagnosed in reproductive aged women with spontaneous ovarian activity. Here we described a case of endometriosis diagnosed in a patient with premature ovarian insufficiency (POI) due to prepubertal bone marrow transplant (BMT). The patient is a 22-year-old nulligravid female who presented with chronic pelvic pain. She had an inherited bone marrow failure syndrome (Diamond-Blackfan anemia), which required gonadotoxic chemotherapy for BMT at a young age prior to puberty. At age 13, she received hormone therapy with transdermal estrogen with subsequent addition of cyclic progestin and was later transitioned to combined oral contraceptive pills (COC). Endometriosis was suspected due to progressive dysmenorrhea and multiple cyclic systemic symptoms. She underwent a trial of elagolix, but could not tolerate it due to worsened arthralgia. Norethindrone acetate (NET-A) was then started, and she underwent diagnostic laparoscopy. Laparoscopy revealed scattered superficial endometriotic lesions in the pelvis. Histological studies showed florid endometriosis. Patient continues on NET-A 10mg and oral estradiol 0.5mg daily since the surgery and has experienced sustained improvement in her symptoms. Endometriosis should be considered as a possible cause for progressive dysmenorrhea or pelvic pain, even in the setting of POI. The balance between HT for overall health benefits in young women with POI and the risk of endometriosis exacerbation is delicate, but achievable., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Localized cutaneous leishmaniasis (LCL) is a chronic ulcerating disease. A literature review identified inconsistencies in clinical trials. The aims of this study were to reach a consensus on the most important domains to measure when assessing LCL, agree on parameters to measure the domains, and develop a tool representing a Core Outcome Set (COS), for use in clinical assessment of LCL., Methodology & Principal Findings: A literature review was conducted to identify any existing COS for LCL embracing agreed Outcome Domains, i.e. what to measure and any Outcome Measurement Instruments (OMIs). As no COS was available, potential outcome domains for assessment of LCL were identified through an international collaborative approach using e-consultations and virtual discussions with expert stakeholders (n = 20) from geographically different LCL endemic countries. Subsequent judgmental validation process included a face-to-face multidisciplinary stakeholders' meeting adopting the Nominal Group Technique. A final consensual agreement on outcome domains and items required to measure these domains was established. "Clinical Cure" was defined as the ideal overall "General Concept". The five Core Outcome Domains included Signs capturing clinical morphology, diameter, and induration of an index lesion with the aid of a palpability score, Treatment Efficacy assessing percentage change in size of the lesion and re-epithelialization compared to baseline, Treatment Impact which included an investigator and patient visual analogue score, and Clinical Sequelae rating pigment change, atrophic and hypertrophic/keloid scars. It was agreed that two open-ended questions should be included to capture some aspects of Health-Related Quality of Life as a means of capturing a patient-focused approach., Conclusion: LeishCOM_LCL was generated to reflect a COS for LCL. This captured demographic details, agreed outcome domains and measures to assess these domains. Validation of LeishCOM_LCL will be reported in a separate paper. Development of a Patient Reported Outcome Measure will be considered in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ranasinghe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Adverse medical events affect 10% of American households annually, inducing a variety of harms and attitudinal changes. The impact of adverse events on perceived abandonment by patients and their care partners has not been methodically assessed., Objective: To identify ways in which providers, patients and families responded to medical mishaps, linking these qualitatively and statistically to reported feelings of abandonment and sequelae induced by perceived abandonment., Methods: Mixed-methods analysis of responses to the Massachusetts Medical Errors Recontact survey with participants reporting a medical error within the past 5 years. The survey consisted of forty closed and open-ended questions examining adverse medical events and their consequences. Respondents were asked whether they felt 'that the doctors abandoned or betrayed you or your family'. Open-ended responses were analysed with a coding schema by two clinician coders., Results: Of the 253 respondents, 34.5% initially and 20% persistently experienced abandonment. Perceived abandonment could be traced to interactions before (18%), during (34%) and after (45%) the medical mishap. Comprehensive post-incident communication reduced abandonment for patients staying with the provider associated with the mishap. However, 68.4% of patients perceiving abandonment left their original provider; for them, post-error communication did not increase the probability of resolution. Abandonment accounted for half the post-event loss of trust in clinicians., Limitations: Survey-based data may under-report the impact of perceived errors on vulnerable populations. Moreover, patients may not be cognizant of all forms of adverse events or all sequelae to those events. Our data were drawn from a single state and time period., Conclusion: Addressing the deleterious impact of persisting abandonment merits attention in programmes responding to patient safety concerns. Enhancing patient engagement in the aftermath of an adverse medical event has the potential to reinforce therapeutic alliances between patients and their subsequent clinicians., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open-label observational study to establish a controlled human infection model (CHIM) of sand fly-transmitted cutaneous leishmaniasis (CL) caused by Leishmania major. Between 24 January and 12 August 2022, we exposed 14 participants to L. major-infected Phlebotomus duboscqi. The primary objective was to demonstrate effectiveness of lesion development (take rate) and safety (absence of CL lesion at 12 months). Secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. Lesion development was terminated by therapeutic biopsy (between days 14 and 42 after bite) in ten participants with clinically compatible lesions, one of which was not confirmed by parasite detection. We estimated an overall take rate for CL development of 64% (9/14). Two of ten participants had one and one of ten participants had two lesion recurrences 4-8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but as expected, scarring due to a combination of CL and the biopsy procedure was evident. All participants were lesion free at >12-month follow-up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This CHIM offers opportunities for vaccine candidate selection based on human efficacy data and for a greater understanding of immune-mediated pathology. ClinicalTrials.gov identifier: NCT04512742 ., (© 2024. The Author(s).)

Context.—: Urinary and Male Genital Tumours is the 8th volume of the World Health Organization Classification of Tumours series, 5th edition. Released in hard copy in September 2022, it presents an update to the classification of male genital and urinary tumors in the molecular age. Building upon previous volumes in this series, significant effort has been made to harmonize terminology across organ systems for biologically similar tumors (eg, neuroendocrine tumors). Genomic terminology has been standardized and genetic syndromes covered more comprehensively. This review presents a concise summary of this volume, highlighting new entities, notable modifications relative to the 4th edition, and elements of relevance to routine clinical practice., Objective.—: To provide a comprehensive update on the World Health Organization classification of urinary and male genital tumors, highlighting updated diagnostic criteria and terminology., Data Sources.—: The 4th and 5th editions of the World Health Organization Classification of Tumours: Urinary and Male Genital Tumours., Conclusions.—: The World Health Organization has made several changes in the 5th edition of the update on urinary and male genital tumors that pathologists need to be aware of for up-to-date clinical practice., (© 2024 College of American Pathologists.)

Context.—: The subspecialty workforce in pathology globally is inadequate for the demands of many modern therapies. The Open Pathology Education Network (OPEN) was formed to augment the global pathology workforce. The International Gynecologic Cancer Society (IGCS) virtual gynecologic-oncology (gyn-onc) fellowship training identified needs for higher-level pathology support., Objective.—: To report on an OPEN-IGCS pilot project to support gyn-onc and pathology education efforts in a developing country., Design.—: Curriculum with learning objectives and content from open sources was assembled. Mentoring sessions included bidirectional case sharing. Trainees received sequential curricula assignments and had options for communication outside mentoring sessions. Pretest and posttest digital slide assessments were included. Mentors attended the gynecology tumor board, allowing for the assessment of quality and accuracy of pathology diagnosis for cases discussed., Results.—: Learners completing the pretest and posttest showed substantial improvement, with 2 practicing pathologists improving their diagnostic scores from 60% to an average of 95%. A third trainee-level participant also improved, but to a lesser degree. Qualitative assessments included increased confidence in presentation and an increased ability to anticipate questions, raise issues of expanded differential diagnoses, and articulate appropriate workup. Observations of clinicians who participated also noted increased confidence in participating pathologists. Secondary value included establishing an expanded network of support in other subspecialties for participants. Pathologic issues at the tumor board decreased, from more than 50% in the first 3 months of study to 0% in the last 3 months of study. The curriculum was embedded into a self-paced learning portal at courses.open-pathology.org., Conclusions.—: The OPEN-IGCS collaboration model shows the potential to provide subspecialty pathology training remotely., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Steroid cell tumors (SCTs) of the ovary are rare and understudied, and as such, uncertainties remain about their malignant potential, as well as clinicopathologic predictors of patient outcome. Based on a multi-institutional cohort of cases, we present findings from the largest study of SCT reported to date. Clinicopathologic data were documented on 115 cases of SCT that were assembled from 17 institutions. The median patient age was 55 years (range: 9 to 84). When measured, preoperative androgen levels were elevated in 84.2% (48/57) of patients. A total of 111 (96.5%) cases were classified as stage I (103 stage IA; 2 stage IB; 6 stage IC). The stage distribution for the remaining 4 patients was as follows: stage II (n = 1), III (n = 3; 1 IIIA, 1 IIIB, 1 IIIC). The median tumor size was 3 cm (range: 0.2 to 22). Cytologic atypia, microscopic tumor necrosis, microscopic tumor hemorrhage, and a mitotic index of >1 mitotic figure/10 high-power fields were present in 52% (60/115), 9.6% (11/115), 37% (43/115), and 19% (22/115) of cases, respectively. Of 115 patients, 7 (6.1%) recurred postexcision, 4 (3.5%) ultimately died of disease, and 10 (8.7%) either recurred, died of disease, or were advanced stage at presentation. The median duration to recurrence postresection was 33 months (range: 23 to 180). Four of the 7 recurrences were stage IA at baseline. Tumor size >4 cm, International Federation of Gynecology and Obstetrics (FIGO) stage ≥IB, tumor necrosis, and tumor hemorrhage were each significantly associated with reduced recurrence-free survival in log-rank tests and univariable Cox models, with age older than 65 years being of marginal significance (hazard ratio [HR]: 5.4, 95% CI: 1.0-30.0, P = 0.05). Multivariable analyses suggested that FIGO stage ≥IB (HR: 27.5, 95% CI: 2.6-290.5), and age older than >65 years (HR: 21.8, 95% CI: 1.6-303.9) were the only parameters that were independently associated with recurrence. Cross-section analyses showed that tumor necrosis, tumor hemorrhage, and larger tumor size were significantly associated with a FIGO stage ≥IB status, which bolstered the conclusion that they are not independent predictors of recurrence. In summary, <10% of SCTs are clinically malignant, a substantially lower frequency than has previously been reported in the literature. Clinicopathologic predictors of patient outcomes that are prospectively applicable in practice could not be definitively established. Recurrences may occur many years (up to 15 y in this study) after primary resection, even in stage IA cases., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Water deficit stress limits net photosynthetic rate (A N ), but the relative sensitivities of underlying processes such as thylakoid reactions, ATP production, carbon fixation reactions, and carbon loss processes to water deficit stress in field-grown upland cotton require further exploration. Therefore, the objective of the present study was to assess (1) the diffusional and biochemical mechanisms associated with water deficit-induced declines in A N and (2) associations between water deficit-induced variation in oxidative stress and energy dissipation for field-grown cotton. Water deficit stress was imposed for three weeks during the peak bloom stage of cotton development, causing significant reductions in leaf water potential and A N . Among diffusional limitations, mesophyll conductance was the major contributor to the A N decline. Several biochemical processes were adversely impacted by water deficit. Among these, electron transport rate and RuBP regeneration were most sensitive to A N -limiting water deficit. Carbon loss processes (photorespiration and dark respiration) were less sensitive than carbon assimilation, contributing to the water deficit-induced declines in A N . Increased energy dissipation via non-photochemical quenching or maintenance of electron flux to photorespiration prevented oxidative stress. Declines in A N were not associated with water deficit-induced variation in ATP production. It was concluded that diffusional limitations followed by biochemical limitations (ETR and RuBP regeneration) contributed to declines in A N , carbon loss processes partially contributed to the decline in A N , and increased energy dissipation prevented oxidative stress under water deficit in field-grown cotton., (© 2024 The Authors. Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.)

The cellular imbalance between high concentrations of ribonucleotides (NTPs) and low concentrations of deoxyribonucleotides (dNTPs), is challenging for DNA polymerases when building DNA from dNTPs. It is currently believed that DNA polymerases discriminate against NTPs through a steric gate model involving a clash between a tyrosine and the 2'-hydroxyl of the ribonucleotide in the polymerase active site in B-family DNA polymerases. With the help of crystal structures of a B-family polymerase with a UTP or CTP in the active site, molecular dynamics simulations, biochemical assays and yeast genetics, we have identified a mechanism by which the finger domain of the polymerase sense NTPs in the polymerase active site. In contrast to the previously proposed polar filter, our experiments suggest that the amino acid residue in the finger domain senses ribonucleotides by steric hindrance. Furthermore, our results demonstrate that the steric gate in the palm domain and the sensor in the finger domain are both important when discriminating NTPs. Structural comparisons reveal that the sensor residue is conserved among B-family polymerases and we hypothesize that a sensor in the finger domain should be considered in all types of DNA polymerases., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Context.—: The World Health Organization Classification of Tumours: Female Genital Tract Tumors, 5th edition, published in September 2020, comes 6 years after the 4th edition, and reflects the monumental leaps made in knowledge about the biology of gynecological tumors. Major changes include revised criteria for the assignment of the site of origin of ovarian and fallopian tube tumors, a revision in the classification of squamous and glandular lesions of the lower genital tract based on human papillomavirus association, and an entire chapter devoted to genetic tumor syndromes. This article highlights the changes in the 5th edition relative to the 4th edition, with a focus on areas of value to routine clinical practice., Objective.—: To provide a comprehensive update on the World Health Organization classification of gynecological tumors, highlighting in particular updated diagnostic criteria and terminology., Data Sources.—: The 4th and 5th editions of the World Health Organization Classification of Tumours., Conclusions.—: The World Health Organization has made several changes in the 5th edition of the update on female genital tumors. Awareness of the changes is needed for pathologists' translation into contemporary practice., (© 2023 College of American Pathologists.)

Cotton (Gossypium hirsutum L.) leafroll dwarf virus disease (CLRDD) is a yield-limiting threat to cotton production and can substantially limit net photosynthetic rates (A N ). Previous research showed that A N was more sensitive to CLRDD-induced reductions in stomatal conductance than electron transport rate (ETR) through photosystem II (PSII). This observation coupled with leaf reddening symptomology led to the hypothesis that differential sensitivities of photosynthetic component processes to CLRDD would contribute to declines in A N and increases in oxidative stress, stimulating anthocyanin production. Thus, an experiment was conducted to define the relative sensitivity of photosynthetic component processes to CLRDD and to quantify oxidative stress and anthocyanin production in field-grown cotton. Among diffusional limitations to A N , reductions in mesophyll conductance and CO 2 concentration in the chloroplast were the greatest constraints to A N under CLRDD. Multiple metabolic processes were also adversely impacted by CLRDD. ETR, RuBP regeneration, and carboxylation were important metabolic (non-diffusional) limitations to A N in symptomatic plants. Photorespiration and dark respiration were less sensitive than photosynthetic processes, contributing to declines in A N in symptomatic plants. Among thylakoid processes, reduction of PSI end electron acceptors was the most sensitive to CLRDD. Oxidative stress indicators (H 2 O 2 production and membrane peroxidation) and anthocyanin contents were substantially higher in symptomatic plants, concomitant with reductions in carotenoid content and no change in energy dissipation by PSII. We conclude that differential sensitivities of photosynthetic processes to CLRDD and limited potential for energy dissipation at PSII increases oxidative stress, stimulating anthocyanin production as an antioxidative mechanism., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Socio-historical barriers remain a concern in Academic Medicine. Regrettably, despite the modern cultural era defined by increased recognition and response to such issues, widespread covert barriers and misperceptions continue to limit the advancement of many, in particular, international medical graduate physicians (IMGs) who represent a significant proportion of the US physician workforce. Adversity is experienced in the form of cultural racism, affinity bias, and underrepresentation in distinct specialties as well as in leadership roles. Often, these unnecessary hardships exacerbate pre-existing discrimination in Academic Medicine, further marginalizing IMGs. In this article, we discuss the prevalence of "medical inferiority bias" and the resulting impact on US healthcare, specifying considerations to be made from a policy perspective., (© 2023 The Authors.)

Lint yield in cotton is governed by light intercepted by the canopy (IPAR), radiation use efficiency (RUE), and harvest index (HI). However, the conventional methods of measuring these yield-governing physiological parameters are labor-intensive, time-consuming and requires destructive sampling. This study aimed to explore the use of low-cost and high-resolution UAV-based RGB and multispectral imagery 1) to estimate fraction of IPAR (IPAR f ), RUE, and biomass throughout the season, 2) to estimate lint yield using the cotton fiber index (CFI), and 3) to determine the potential use of biomass and lint yield models for estimating cotton HI. An experiment was conducted during the 2021 and 2022 growing seasons in Tifton, Georgia, USA in randomized complete block design with five different nitrogen treatments. Different nitrogen treatments were applied to generate substantial variability in canopy development and yield. UAV imagery was collected bi-weekly along with light interception and biomass measurements throughout the season, and 20 different vegetation indices (VIs) were computed from the imagery. Generalized linear regression was performed to develop models using VIs and growing degree days (GDDs). The IPAR f models had R 2 values ranging from 0.66 to 0.90, and models based on RVI and RECI explained the highest variation (93%) in IPAR f during cross-validation. Similarly, cotton above-ground biomass was best estimated by models from MSAVI and OSAVI. Estimation of RUE using actual biomass measurement and RVI-based IPAR f model was able to explain 84% of variation in RUE. CFI from UAV-based RGB imagery had strong relationship (R 2 = 0.69) with machine harvested lint yield. The estimated HI from CFI-based lint yield and MSAVI-based biomass models was able to explain 40 to 49% of variation in measured HI for the 2022 growing season. The models developed to estimate the yield-contributing physiological parameters in cotton showed low to strong performance, with IPAR f and above-ground biomass having greater prediction accuracy. Future studies on accurate estimation of lint yield is suggested for precise cotton HI prediction. This study is the first attempt of its kind and the results can be used to expand and improve research on predicting functional yield drivers of cotton., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pokhrel, Virk, Snider, Vellidis, Hand, Sintim, Parkash, Chalise, Lee and Byers.)

Competing Interests: The authors have no relevant financial interest in the products or companies described in this article.

Cotton breeding programs have focused on agronomically-desirable traits. Without targeted selection for tolerance to high temperature extremes, cotton will likely be more vulnerable to environment-induced yield loss. Recently-developed methods that couple chlorophyll fluorescence induction measurements with temperature response experiments could be used to identify genotypic variation in photosynthetic thermotolerance of specific photosynthetic processes for field-grown plants. It was hypothesized that diverse cotton genotypes would differ significantly in photosynthetic thermotolerance, specific thylakoid processes would exhibit differential sensitivities to high temperature, and that the most heat tolerant process would exhibit substantial genotypic variation in thermotolerance plasticity. A two-year field experiment was conducted at Tifton and Athens, Georgia, USA. Experiments included 10 genotypes in 2020 and 11 in 2021. Photosynthetic thermotolerance for field-collected leaf samples was assessed by determining the high temperature threshold resulting in a 15% decline in photosynthetic efficiency (T 15 ) for energy trapping by photosystem II (Φ Po ), intersystem electron transport (Φ Eo ), and photosystem I end electron acceptor reduction (Φ Ro ). Significant genotypic variation in photosynthetic thermotolerance was observed, but the response was dependent on location and photosynthetic parameter assessed. Φ Eo was substantially more heat sensitive than Φ Po or Φ Ro . Significant genotypic variation in thermotolerance plasticity of Φ Eo was also observed. Identifying the weakest link in photosynthetic tolerance to high temperature will facilitate future selection efforts by focusing on the most heat-susceptible processes. Given the genotypic differences in environmental plasticity observed here, future research should evaluate genotypic variation in acclimation potential in controlled environments., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John Snider reports financial support was provided by Georgia Cotton Commission. John Snider reports financial support was provided by National Science Foundation., (Copyright © 2023. Published by Elsevier Masson SAS.)

Context.—: Despite widely prevalent burnout and attendant disengagement in medicine, the specific patterns and drivers within pathology and laboratory medicine are uncommonly studied., Objective.—: To assess the prevalence and drivers of burnout among pathology and laboratory medicine professionals, retrospectively, prior to the COVID-19 pandemic., Design.—: This was a cross-sectional, mixed-methods study engaging pathology and laboratory medicine professionals as subjects., Results.—: Of 2363 respondents, 438 identified as pathologists, 111 as pathology assistants, and 911 as pathology and laboratory professionals. The burnout rate was 58.4% (1380 of 2363) across all respondents in pathology and laboratory medicine. Burnout varied by job role (P < .01) and was highest among pathology and laboratory professionals. Disparities in burnout rate were observed by race. Fifty-six percent (1323 of 2363) of respondents felt that they had at least 1 symptom of burnout and were advancing toward a breaking point. Underlying factors ranked highly among all groups included control over workload and loss of meaning in work., Conclusions.—: Data provided from this cohort may help departments create successful strategies to reduce disengagement and burnout in the laboratory, especially during periods of increased stress as experienced during the COVID-19 pandemic. Further, these data may serve as a baseline comparison for future studies., (© 2023 College of American Pathologists.)

We describe a very unusual cervical tumor in a 12-yr-old patient with a clinical history indicative of DICER1 syndrome. Morphologic, immunohistochemical, and molecular genetic analysis together helped to diagnose this lesion as a cervical pleuropulmonary blastoma-like tumor, associated with TP53 and DICER1 mutations. The tumor displayed usual histologic features including mixtures of embryonal rhabdomyosarcoma, sarcomatous cartilage, compact blastema, primitive spindle cells and anaplasia, akin to type III pleuropulmonary blastoma, and trabecular and retiform patterns. In addition to expanding the phenotypic spectrum of DICER1 -associated conditions, we draw attention to genotype-phenotype correlations in DICER1 -associated tumors, particularly as they relate to the discovery of a heritable tumor predisposition syndrome., Competing Interests: B.W. reports ad hoc membership of the scientific advisory board of Repare Therapeutics, outside the scope of the submitted work. The remaining authors declare no conflict of interest., (Copyright © 2022 by the International Society of Gynecological Pathologists.)

Background: Leishmaniasis is a neglected tropical disease that is imported by travellers returning to the UK. Given the prolonged therapy required, outpatient treatment has been proven to be cost-effective and safe., Methods: We describe cases of leishmaniasis treated through outpatient parenteral antimicrobial therapy (OPAT) over a 13-y period (March 2006-September 2018) at a large teaching hospital., Results: A total of 26 episodes of leishmaniasis were treated successfully, with a mean saving of 14.2 bed-days/episode. Sodium stibogluconate was the most used antileishmanial (92%)., Conclusions: Treatment of chronic infections via OPAT is now commonplace and this approach may be considered for other imported infectious diseases., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Nitrogen (N) deficiency limits the net carbon assimilation rate (AN), but the relative N sensitivities of photosynthetic component processes and carbon loss mechanisms remain relatively unexplored for field-grown cotton. Therefore, the objective of the current study was to define the relative sensitivity of individual physiological processes driving N deficiency-induced declines in AN for field-grown cotton. Among the potential diffusional limitations evaluated, mesophyll conductance was the only parameter substantially reduced by N deficiency, but this did not affect CO2 availability in the chloroplast. A number of metabolic processes were negatively impacted by N deficiency, and these effects were more pronounced at lower leaf positions in the cotton canopy. Ribulose bisphosphate (RuBP) regeneration and carboxylation, AN, and gross photosynthesis were the most sensitive metabolic processes to N deficiency, whereas photosynthetic electron transport processes, electron flux to photorespiration, and dark respiration exhibited intermediate sensitivity to N deficiency. Among thylakoid-specific processes, the quantum yield of PSI end electron acceptor reduction was the most sensitive process to N deficiency. It was concluded that AN is primarily limited by Rubisco carboxylation and RuBP regeneration under N deficiency in field-grown cotton, and the differential N sensitivities of the photosynthetic process and carbon loss mechanisms contributed significantly to photosynthetic declines., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The World Health Organization (WHO) has created a sustainable development goal of reducing preventable mortality from cancer in low- and middle-income countries (LMICs) by 30% by 2030. Central to achieving this goal is the creation and maintenance of quality anatomic pathology services (APS). Within the last decade, quality assurance programs and patient safety measures have become a major focus of research for upper middle- and high-income countries (UMHICs), which has led to marked documented improvement in the quality of services provided by laboratories, as well as a decrease in patient safety events. We propose that as APS are developed in LMICs, the lessons learned by UMHICs are necessary to incorporate to produce quality and safe services toward obtaining the aforementioned goal. Furthermore, data suggests that Quality Improvement work requires change at the macrosystems and microsystems levels to achieve these goals. Here, we propose five "microsystems" strategies for professional organizations, healthcare institutions in LMICs and UMHICs that would accelerate quality improvement programs/systems implementation in APS in LMICs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Smith, Eadara and Parkash.)

Amino acid substitutions in the exonuclease domain of DNA polymerase ϵ (Polϵ) cause ultramutated tumors. Studies in model organisms suggested pathogenic mechanisms distinct from a simple loss of exonuclease. These mechanisms remain unclear for most recurrent Polϵ mutations. Particularly, the highly prevalent V411L variant remained a long-standing puzzle with no detectable mutator effect in yeast despite the unequivocal association with ultramutation in cancers. Using purified four-subunit yeast Polϵ, we assessed the consequences of substitutions mimicking human V411L, S459F, F367S, L424V and D275V. While the effects on exonuclease activity vary widely, all common cancer-associated variants have increased DNA polymerase activity. Notably, the analog of Polϵ-V411L is among the strongest polymerases, and structural analysis suggests defective polymerase-to-exonuclease site switching. We further show that the V411L analog produces a robust mutator phenotype in strains that lack mismatch repair, indicating a high rate of replication errors. Lastly, unlike wild-type and exonuclease-dead Polϵ, hyperactive variants efficiently synthesize DNA at low dNTP concentrations. We propose that this characteristic could promote cancer cell survival and preferential participation of mutator polymerases in replication during metabolic stress. Our results support the notion that polymerase fitness, rather than low fidelity alone, is an important determinant of variant pathogenicity., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: To examine the prevalent understanding of and management approaches to chronic endometritis among obstetricians/gynecologists., Methods: In a cross-sectional observational study, 262 members of national and international professional obstetrician/gynecologist societies were surveyed via anonymous electronic survey that investigated knowledge of the pathophysiology, diagnostic criteria, clinical implications, and treatment strategies for chronic endometritis. Statistical analyses of results were performed using Fisher's exact tests, chi square tests and odds ratios with 95% confidence intervals. A two-sided P < 0.05 was deemed statistically significant., Results: Responses identified a concerning spectrum of deficiencies in the understanding of the pathophysiology of chronic endometritis, in awareness of clinical presentation of chronic endometritis, and in the understanding of methodology/ies that allow diagnosis of chronic endometritis. Heterogeneities in management approaches to chronic endometritis were apparent., Conclusion: Our findings underscore a need for targeted efforts to gain clarity on chronic endometritis and to establish evidence-based consensus for good clinical practice. In the absence of a clear understanding of chronic endometritis diagnosis, we posit that the prevalent inconsistencies are likely inflicting unquantified and underappreciated burdens on patients and healthcare systems. We propose consideration for a task force to examine existing literature and create standards for good practice for a prevalent condition., (© 2021 International Federation of Gynecology and Obstetrics.)

Patients with germline TP53 mutations are characterized by the occurrence of multiple early-onset malignancies. The characteristic syndrome is Li-Fraumeni syndrome (OMIM # 151623), an autosomal dominant disorder typified by premenopausal breast carcinoma, adrenal cortical tumors, bone and soft tissue sarcomas, leukemias, and tumors of the brain and spinal cord. Gynecologic malignancies are uncommonly reported in families harboring TP53 mutations, and the predominant tumor type reported is ovarian. Uterine carcinoma has been reported only a handful of times in patients with germline TP53 mutations, none as a presenting tumor in a teenager. We report on an 18-year-old patient who presented with grade 3, high-stage endometrioid endometrial carcinoma. Sequencing detected a single-nucleotide substitution in the TP53 gene (NM&#95;000546.6:c.818G>A), encoding the missense substitution p.Arg273His (R273H) in both the tumor and normal tissue, consistent with a germline mutation. We discuss the biology of the TP53 gene and p53 protein, with emphasis on the R273H mutation. We also review the literature on endometrial carcinoma in patients with germline TP53 mutations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)