bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of dynamic explosive resistance exercise with elastic bands on pulse pressure in hypertensive older adults: a randomized crossover study
Authors: Bavaresco Gambassi Bruno , Nobre Izadora , Prazeres Jozimar , de Melo Maycon Henrique , Bianco Roberto , Novais Tânia Maria , Oliveira Paula de Lourdes , Souza Thiago Antonio , Ribeiro Maria Jacqueline , Schwingel Paulo Adriano
Published: May 2023

Objective

This study aimed to evaluate the acute responses of pulse pressure (PP), SBP, and DBP to dynamic explosive resistance exercise (DERE) with elastic resistance bands in hypertensive older adults.

Methods

Eighteen hypertensive older adults were randomly assigned to participate in DERE and control sessions. PP, SBP, and DBP were measured before (baseline) and after each session (immediately, 10, and 20 min after the session). The DERE protocol has five sets of two consecutive exercises.

Results

There was an important clinical decrease in PP (Δ = −7.8 mmHg; d

z
= 0.7) and in DBP (Δ = −6.3 mmHg; d
z = 0.6) favoring the exercise session post-20 min in the intersession comparison. DERE also promoted lowering levels in SBP (140.3 ± 16.0 vs. 126.2 ± 14.3 mmHg; Δ = −14.1 mmHg; P = 0.04) with a large effect size (d

z
= 0.9) post-20 min when compared to the control session.

Conclusion

Our findings indicate that DERE with elastic resistance bands improved SBP in hypertensive older adults. In addition, our results support the hypothesis that DERE can an important clinical decrease in PP and DBP. According to this, professionals may have additional exercise training possibilities with elastic resistance bands when prescribing resistance exercises for systemic arterial hypertension treatment in this population.
DEGS1-related leukodystrophy: a clinical report and review of literature
Authors: Wong Melissa Song Ting , Thomas Terrence , Lim Jiin Ying , Kam Sylvia , Teo Jing Xian , Ching Jianhong , Goh Chew Yin Jasmine , Jamuar Saumya Shekhar , Lim Weng Khong , Koh Ai Ling
Published: May 2023

Background:

Leukodystrophies are a heterogeneous group of disorders affecting the white matter of the central nervous system, with or without affecting the peripheral nervous system. Biallelic variants in DEGS1, coding for desaturase 1 (Des1) protein, were recently reported to be associated with hypomyelinating leukodystrophy (HLD), a subclass of leukodystrophies where the formation of the myelin sheath is affected.

Methods

Genomic sequencing was performed on our index patient with severe developmental delay, severe failure to thrive, dystonia, seizures, and hypomyelination on brain imaging. Sphingolipid analysis was performed and dihydroceramide/ceramide (dhCer/Cer) ratios were obtained by the measurement of ceramide and dihydroceramide species.

Results

A homozygous missense variant was identified in DEGS1 (c.565A > G:p Asn189Asp). The identified DEGS1 variant has been annotated as “conflicting reports of pathogenicity” on ClinVar. Follow-up sphingolipid analysis on our patient showed significantly raised dhCer/Cer and this was consistent with dysfunction of the Des1 protein, providing additional evidence to support the pathogenicity of this variant.

Conclusion

While rare, pathogenic variants in DEGS1 should be considered in patients with HLD phenotype. To date, 25 patients have been reported across four studies on DEGS1-related HLD, and, in this report, we summarize the literature. More such reports will enable deeper phenotypic characterization of this disorder.
Mechanisms and clinical applications of incretin therapies for diabetes and chronic kidney disease
Authors: Alicic Radica Z. , Neumiller Joshua J. , Tuttle Katherine R.
Published: May 2023

Purpose of review

Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide. Development of DKD increases risks for cardiovascular events and death. Glucagon-like peptide-1 (GLP-1) receptor agonist have demonstrated improved cardiovascular and kidney outcomes in large-scale clinical trials.

Recent finding

GLP-1 and dual GLP-1/glucose-depending insulinotropic polypeptide (GIP) receptor agonists have robust glucose-lowering efficacy with low risk of hypoglycemia even in advanced stages of DKD. Initially approved as antihyperglycemic therapies, these agents also reduce blood pressure and body weight. Cardiovascular outcome and glycemic lowering trials have reported decreased risks of development and progression of DKD and atherosclerotic cardiovascular events for GLP-1 receptor agonists. Kidney and cardiovascular protection is mediated partly, but not entirely, by lowering of glycemia, body weight, and blood pressure. Experimental data have identified modulation of the innate immune response as a biologically plausible mechanism underpinning kidney and cardiovascular effects.

An influx of incretin-based therapies has changed the landscape of DKD treatment. GLP-1 receptor agonist use is endorsed by all major guideline forming organizations. Ongoing clinical trials and mechanistic studies with GLP-1 and dual GLP-1/GIP receptor agonists will further define the roles and pathways for these agents in the treatment of DKD.
Fibroblast growth factor 23, klotho and heparin
Authors: Thomas S. Madison , Li Qing , Faul Christian
Published: May 2023

Purpose of review

Fibroblast growth factor (FGF) 23 is a bone-derived hormone that regulates phosphate and vitamin D metabolism by targeting the kidney. When highly elevated, such as in chronic kidney disease (CKD), FGF23 can also target the heart and induce pathologic remodeling. Here we discuss the mechanisms that underlie the physiologic and pathologic actions of FGF23, with focus on its FGF receptors (FGFR) and co-receptors.

Recent findings

Klotho is a transmembrane protein that acts as an FGFR co-receptor for FGF23 on physiologic target cells. Klotho also exists as a circulating variant, and recent studies suggested that soluble klotho (sKL) can mediate FGF23 effects in cells that do not express klotho. Furthermore, it has been assumed that the actions of FGF23 do not require heparan sulfate (HS), a proteoglycan that acts as a co-receptor for other FGF isoforms. However, recent studies revealed that HS can be part of the FGF23:FGFR signaling complex and modulate FGF23-induced effects.

sKL and HS have appeared as circulating FGFR co-receptors that modulate the actions of FGF23. Experimental studies suggest that sKL protects from and HS accelerates CKD-associated heart injury. However, the in vivo relevance of these findings is still speculative.
Direct-to-consumer STI screening methods: Preferred communication sources and channels among young adult women
Authors: Griner Stacey B. , Johnson Kaeli C. , Neelamegam Malinee , Webb Nathaniel J. , Kinard Ashlyn , Kline Nolan
Published: May 2023

Background

Direct-to-consumer (DTC) sexually transmitted infection (STI) screening methods utilize self-collected samples in a non-clinical setting. DTC methods may reach a population of women who avoid screening due to stigma, privacy concerns, or who lack access to clinical care. Little is known about the salient dissemination approaches to promote these methods. The study’s purpose was to identify preferred sources and communication channels for information about DTC methods among young adult women.

Methods

Participants were sexually active 18–24-year-old college women at one university, recruited via purposive sampling using campus email, list-servs, and campus events to participate in an online survey (n = 92). Interested participants were invited to participate in in-depth interviews (n = 24). Both instruments were guided by the Diffusion of Innovation theory to identify relevant communication channels.

Results

Survey participants ranked healthcare providers as their preferred source of information, followed by the internet and college- and university-based resources. Race was significantly associated with the ranking of partners and family members as information sources. Interview themes focused on healthcare providers legitimizing DTC methods, using the internet and social media to increase awareness, and linking DTC method education to other services provided by the college.

Conclusion

This study revealed common information sources that college-age women may utilize when researching DTC method information and potential channels and strategies for DTC uptake and dissemination. Utilizing trusted sources including healthcare providers, trusted websites, and established college resources as dissemination channels may be beneficial to increase the awareness and use of DTC methods for STI screening.
Human papillomavirus positivity at three anatomical sites among transgender women in Central Brazil
Authors: de Oliveira Brunna Rodrigues , Diniz e Silva Bruno Vinícius , dos Santos Kamila Cardoso , Caetano Karlla Antonieta Amorim , Mota Giana , Saddi Vera Aparecida , dos Santos Silvia Helena Rabelo , Villa Luisa Lina , Vaddiparti Krishna , Cook Robert L. , Teles Sheila Araujo , Carneiro Megmar Aparecida dos Santos
Published: May 2023

Background

Transgender women (TGWs) are susceptible to the acquisition of sexually transmitted infections (STIs), including human papillomavirus (HPV). Nonetheless, the exact data for this population are scarce. We estimated HPV positivity at the anal, genital, and oral sites among TGWs and also identified the related characteristics and behaviors that could be risk factors for HPV infection in a sample of TGWs in Brazil. Furthermore, we characterized the site-specific HPV genotypes among those who were positive for HPV at these three sites.

Methods: A cross-sectional study was conducted on TGWs in Goiânia City (Central–Midwest region), Brazil, between April 2018 and August 2019. Respondent-driven sampling was applied for recruitment. Next, self-collected anal, genital, and oral samples were examined for HPV DNA using polymerase chain reaction (SPF-10 primer). HPV genotypes were identified in 12 TGWs.

Results

In the TGWs included in the study, the anal, genital, and oral HPV positivity was 77.2% (95% CI: 67.3–84.6), 33.5% (95% CI: 26.1–48.9), and 10.9% (95% CI: 5.8–17.0), respectively. Additionally, the majority of 12 participants who tested for HPV had multiple genotypes. HPV-52 was the most prevalent genotype identified at the anal (66.6%) and genital (40.0%) sites, whereas HPV-62 and HPV-66 were the most common at the oral site (25.0%).

Conclusions

A high HPV positivity was observed among TGWs. Therefore, additional epidemiological studies on HPV genotypes should generate health intervention information, including the prevention, diagnosis, and treatment of STIs.
Family Support, Open Communication, and Black Gay and Bisexual Young Men’s Attitudes and Stigma Around Pre-Exposure Prophylaxis
Authors: Boyd Donte , Abu-Ba’are Gamji Rabiu , Zigah Edem Yaw , Williams Antonio T. , Flores Dalmacio D.
Published: May 2023

Purpose

This study addresses the gap in the literature on protective factors for Pre-exposure prophylaxis (PrEP) stigma and attitudes among Black men who have sex with men (BMSM) and young adults using the Developmental Assets Framework to examine how external assets (e.g., family support, open family communication, and communication with parents about sex and drugs) can help reduce stigma and increase positive attitudes toward PrEP use.

Methods

A cross-sectional survey was administered to participants (N = 400, mean age = 23.46, standard deviation =2.59) using Amazon Mechanical Turk, social media sites, and community-based organization. A path analysis was conducted to examine associations between stigma and positive attitudes toward PrEP among external assets (family support, communication with parents about sex and drugs, and open family communication).

Results

Communication with parents about sex and drugs was positive and directly associated with PrEP stigma (β = 0.42, p < .001). Family support was negative and indirectly associated with stigma associated with PrEP (β = −0.20, p < .001).

Conclusion

This is the first study to use a developmental asset framework to assess positive PrEP attitudes and stigma among young BMSM. Our results underscore that parents have an influence on HIV prevention behaviors for BMSM. In addition, their influence can be both positive by helping lowering PrEP stigma and negatively lowering PrEP attitudes. It’s critical that we develop culturally competent HIV and sexuality prevention and intervention programs for BMSM and their families.
Evaluating the impact of the COVID-19 related public health restrictions on access to digital sexually transmitted and blood borne infection testing in British Columbia, Canada: An interrupted time series analysis
Authors: Iyamu Ihoghosa , Pedersen Heather , Ablona Aidan , Chang Hsiu-Ju , Worthington Cathy , Grace Daniel , Grennan Troy , Wong Jason , Salmon Amy , Koehoorn Mieke , Gilbert Mark
Published: May 2023

Background

Evidence of long-term impacts of COVID-19 related public health restrictions on digital sexually transmitted and blood borne infection (STBBI) testing utilization is limited. We assessed these impacts onGetCheckedOnline(a digital testing resource for STBBIs) relative to all STBBI tests in British Columbia (BC).

Methods

Interrupted time series analyses were conducted usingGetCheckedOnlineprogram data comparing monthly test episodes (STBBI tests per requisition) among BC residents, stratified by BC region, testers’ sociodemographic and sexual risk profiles, for the pre-pandemic (March 2018-February 2020) and pandemic periods (March 2020-October 2021). Trends inGetCheckedOnlinetesting per 100 STBBI tests in BC regions withGetCheckedOnlinewere analysed. Each outcome was modelled using segmented generalized least squared regression.

Results

Overall, 17,215 and 22,646 test episodes were conducted in the pre-pandemic and pandemic periods. MonthlyGetCheckedOnlinetest episodes reduced immediately after restrictions. By October 2021(end of pandemic period), monthlyGetCheckedOnlinetesting increased 21.24 test episodes per million BC residents (95%CI: -11.88, 54.84) andGetCheckedOnlinetests per 100 tests in corresponding BC regions increased 1.10 (95%CI: 0.02, 2.17) above baseline trends. After initial increases among users at higher STBBI risk (symptomatic testers/testers reporting sexual contacts with STBBIs), testing decreased below baseline trends later in the pandemic, while monthlyGetCheckedOnlinetesting increased among people ≥40 years, men who have sex with men, racialized minorities, and first-time testers viaGetCheckedOnline.

Conclusions

Sustained increases in utilization of digital STBBI testing during the pandemic suggest fundamental changes in STBBI testing in BC, highlighting the need for accessible and appropriate digital testing, especially for those most affected by STBBIs.
Updates in Risk Stratification in Myelodysplastic Syndromes
Authors: Aguirre Luis E. , Sallman David A. , Stone Richard , Komrokji Rami S.
Published: May 2023

Risk stratification plays an essential role in treatment planning in myelodysplastic syndromes. For decades, the International Prognostic Scoring System and its revised version have provided unified consensus for clinical trial enrollment and design. These models relied on laboratory and cytogenetic data to estimate prognosis and dictate treatment paradigms. Critical developments in DNA sequencing techniques in recent years, as well as our growing understanding of the clonal dynamics of myelodysplastic syndromes and the role that specific mutations have in shaping disease-specific phenotypes and treatment susceptibilities, have made it possible to identify molecular markers that carry critical diagnostic and therapeutic relevance and remained unaccounted for in the older models. The Molecular International Prognostic Scoring System is a novel risk stratification model that integrates clinical, cytogenetic, and molecular data to devise a more refined prognostic tool that builds on the accuracy of the traditional models.
Germline Predisposition to Myelodysplastic Syndromes
Authors: Gener-Ricos Georgina , Gerstein Yoheved S. , Hammond Danielle , DiNardo Courtney D.
Published: May 2023

While germline predisposition to myelodysplastic syndromes is well-established, knowledge has advanced rapidly resulting in more cases of inherited hematologic malignancies being identified. Understanding the biological features and main clinical manifestations of hereditary hematologic malignancies is essential to recognizing and referring patients with myelodysplastic syndrome, who may underlie inherited predisposition, for appropriate genetic evaluation. Importance lies in individualized genetic counseling along with informed treatment decisions, especially with regard to hematopoietic stem cell transplant–related donor selection. Future studies will improve comprehension of these disorders, enabling better management of affected patients and their families.
Evolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms
Authors: Stempel Jessica M. , Xie Zhuoer , Bewersdorf Jan Philipp , Stahl Maximilian , Zeidan Amer M.
Published: May 2023

Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous, clonal myeloid neoplasms characterized by ineffective hematopoiesis, progressive cytopenias, and an increased risk of progression to acute myeloid leukemia. The diversity in disease severity, morphology, and genetic landscape challenges not only novel drug development but also therapeutic response assessment. The MDS International Working Group (IWG) response criteria were first published in the year 2000 focusing on measures of blast burden reduction and hematologic recovery. Despite revision of the IWG criteria in 2006, correlation between IWG-defined responses and patient-focused outcomes, including long-term benefits, remains limited and has potentially contributed to failures of several phase III clinical trials. Several IWG 2006 criteria also lacked clear definitions leading to problems in practical applications and interobserver and intraobserver consistency of response reporting. Although the 2018 revision addressed lower-risk MDS, the most recent update in 2023 redefined responses for higher-risk MDS and has set out to provide clear definitions to enhance consistency while focusing on clinically meaningful outcomes and patient-centered responses. In this review, we analyze the evolution of the MDS response criteria, limitations, and areas of improvement.
Effectiveness of topical cidofovir for treatment of refractory anal high-grade squamous intraepithelial lesion (HSIL)
Authors: Burgos Joaquin , Campany David , Garcia Jorge , Landolfi Stefania , Falcó Vicenç , Curran Adrià
Published: May 2023

Objectives:

Ablative electrocautery is effective treating anal high-grade squamous intraepithelial lesions (HSIL). However, persistence or recurrence of the HSIL despite ablative sessions is not uncommon. The aim of this study is to assess the feasibility of topical cidofovir as salvage therapy for the management of refractory HSIL

Design:

A prospective un-controlled unicenter study of men and transgender people who have sex with men with HIV who had a refractory intra-anal HSIL after ablative treatments and who received topical cidofovir (ointment at 1%, auto-applicated, three times a week, a total of 8 weeks) as salvage therapy. Effectiveness was evaluated on-treatment defining response as resolution or regression to low-grade lesion of HSIL in the biopsy post-treatment. Tolerance and recurrences were recorded.

Results:

From 2017 to 2022, 23 patients with refractory intra-anal HSIL (78.3% persistent lesions, 39% affecting > 50% of circumference and a median of 6 previous ablative sessions) were treated with topical cidofovir. A response was observed in 16 of 23 patients (69.5% [95% CI; 50.8–88.4]). Local tolerance was reported as regular or bad in 13 patients (52.2%), requiring modification of the treatment in 8 patients (3 early discontinuation and 5 dose reduction). Non serious side-effects were reported. After a median follow-up of 30.3 months, 2 of the 16 patients with a response developed recurrent HSIL (Recurrence rate, 25.4% at 12 months [95% CI, 0–35]).

Conclusions:

Topical cidofovir could be a good option in the management of anal HSIL due to its good effectiveness, low recurrence rate, and acceptable tolerance even in difficult-to-treat lesions.
Sex differences in incident atherosclerotic cardiovascular disease events among women and men living with HIV
Authors: Wise Jenni M. , Jackson Elizabeth A. , Kempf Mirjam-Colette , Oates Gabriela R. , Wang Zhixin , Overton Edgar T. , Siddiqui Mohammed , Woodward Mark , Rosenson Robert S. , Muntner Paul
Published: May 2023

Background:

The protective advantage against atherosclerotic cardiovascular disease (ASCVD) experienced by women compared to men in the general population is diminished in some high- risk populations. People living with HIV have a higher risk for ASCVD compared to the general population.

Objective:

Compare the incidence of ASCVD among women versus men living with HIV.

Methods:

We analyzed data from women (n = 17,118) versus men (n = 88,840) with HIV, and women (n = 68,472) and men (n = 355,360) matched on age, sex, and calendar year of enrollment without HIV who had commercial health insurance in the MarketScan database between 2011 and 2019. ASCVD events during follow-up, including myocardial infarction, stroke, and lower- extremity artery disease, were identified using validated claims-based algorithms.

Results:

Among those with and without HIV, the majority of women (81.7%) and men (83.6%) were <55 years old. Over a mean follow-up of 2.25 to 2.36 years depending on sex-HIV sub- group, the ASCVD incidence rate per 1,000 person-years was 2.87 (95%CI 2.35, 3.40) and 3.61 (3.35, 3.88) among women and men living with HIV, respectively, and 1.24 (1.07, 1.42) and

2.57 (2.46, 2.67) among women and men without HIV, respectively. After multivariable adjustment, the hazard ratio for ASCVD comparing women to men was 0.70 (95%CI 0.58, 0.86) among those with HIV and 0.47 (0.40, 0.54) among those without HIV (p-interaction = 0.001).

Conclusion:

The protective advantage of female sex against ASCVD observed in the general population is diminished among women living with HIV. Earlier and more intensive treatment strategies are needed to reduce sex-based disparities.
Cognitive concerns are a risk factor for mortality in people with human immunodeficiency virus and COVID-19
Authors: Wilcox Douglas R. , Rudmann Emily A. , Ye Elissa , Noori Ayush , Magdamo Colin , Jain Aayushee , Alabsi Haitham , Foy Brody , Triant Virginia A. , Robbins Gregory K. , Westover M. Brandon , Das Sudeshna , Mukerji Shibani S.
Published: May 2023

Background:

Data supporting dementia as a risk factor for COVID-19 mortality relied on ICD-10 codes, yet nearly 40% of individuals with probable dementia lack a formal diagnosis. Dementia coding is not well-established for people with HIV (PWH), and its reliance may affect risk assessment.

Methods:

This retrospective cohort analysis of PWH with SARS-CoV-2 polymerase chain reaction positivity includes comparisons to people without HIV (PWoH), matched by age, sex, race, and zipcode. Primary exposures were dementia diagnosis, by ICD-10 codes, and cognitive concerns, defined as possible cognitive impairment up to 12 months before COVID-19 diagnosis after clinical review of notes from the electronic health record. Logistic regression models assessed the effect of dementia and cognitive concerns on odds of death (OR [95% confidence interval]); models adjusted for VACS Index 2.0.

Results:

Sixty-four PWH were identified out of 14,129 patients with SARS-CoV-2 infection and matched to 463 PWoH. Compared to PWoH, PWH had a higher prevalence of dementia (15.6% vs. 6%, p = 0.01) and cognitive concerns (21.9% vs. 15.8%, p = 0.04). Death was more frequent in PWH (p < 0.01). Adjusted for VACS Index 2.0, dementia (2.4 [1.0–5.8], p = 0.05) and cognitive concerns (2.4 [1.1–5.3], p = 0.03) were associated with increased odds of death. In PWH, the association between cognitive concern and death trended towards statistical significance (3.92 [0.81–20.19], p = 0.09); there was no association with dementia.

Conclusions:

Cognitive status assessments are important for care in COVID-19, especially among PWH. Larger studies should validate findings and determine long-term COVID-19 consequences in PWH with pre-existing cognitive deficits.
Effects of Pure Barre Exercise on Urinary Incontinence Symptoms: A Prospective Observational Cross-Sectional Study
Authors: Briskin Rebeccah S. , Luck Ali M.
Published: May 2023

Importance

Pure Barre is a form of physical exercise using low-impact, high-intensity, pulsatile isometric movements that may serve as a treatment option for urinary incontinence.

Objective

The objective of this study was to measure the effects of the Pure Barre workout on urinary incontinence symptoms and sexual function.

Study Design

This was a prospective observational study of new, female Pure Barre clients with urinary incontinence. Eligible participants completed 3 validated questionnaires at baseline and at follow-up after 10 Pure Barre classes within 2 months. Questionnaires included the Michigan Incontinence Symptoms Index (M-ISI), the Pelvic Floor Distress Inventory-20, and the Female Sexual Function Index-6. Matched differences in domain questionnaire scores between baseline and follow-up were analyzed.

Results

All questionnaire domains significantly improved for all 25 participants after 10 Pure Barre classes. Median M-ISI severity domain scores decreased from 13 (interquartile range, 9–19) at baseline to 7 at follow-up (interquartile range, 3–10; P < 0.0001). Mean ± SD M-ISI urgency urinary incontinence domain scores decreased from 6.40 ± 3.06 to 2.96 ± 2.13 (P < 0.0001). Mean ± SD M-ISI stress urinary incontinence scores decreased from 5.24 ± 2.71 to 2.48 ± 1.58 (P < 0.0001). Mean ± SD Urinary Distress Inventory domain scores decreased from 42.17 ± 17.15 to 29.67 ± 13.73 (P < 0.0001). Matched rank sum analysis indicated increasing Female Sexual Function Index-6 scores from baseline to follow-up (P = 0.0022).

Conclusion

The Pure Barre workout may be an enjoyable, conservative management option that improves symptoms of urinary incontinence and sexual function.
Clean-Catch Urine Specimen More Likely to Be Contaminated After Vaginal Surgery for Pelvic Organ Prolapse
Authors: O’Meara Amanda , Abalyan Victoria , O’Sullivan David M. , Tunitsky-Bitton Elena
Published: May 2023

Importance

Accurate diagnosis of urinary tract infection after pelvic organ prolapse (POP) surgery is essential to postoperative care.

Objective

Our aim was to determine the agreement between the urinalysis of a clean-catch versus a straight catheter urine specimen in women who underwent vaginal surgery for POP.

Study Design

This was a cross-sectional study evaluating patients after vaginal surgery for POP. A clean-catch and straight catheter urine specimen were collected at routine postoperative appointments. Routine urinalyses and urine cultures were performed for all patients. A urine culture yielding mixed urogenital flora (which includes Lactobacillus species), coagulase-negative staphylococci, and Streptococcus species was considered a contaminated result. The agreement between the characteristics of urinalysis obtained via the clean catch versus the straight catheter at 3 weeks postoperatively was evaluated using weighted κ statistic.

Results

Fifty-nine participants enrolled. The agreement between the characteristics of urinalysis obtained via the clean catch versus the straight catheter was poor (κ = 0.018). The urine culture was more likely to be contaminated from the clean-catch urine specimen than from the straight catheter urine specimen (53.7% vs 23.1%).

The positive and negative predictive values of leukocyte esterase on clean catch were 22.6% and 100%, respectively.

Conclusions

Diagnosing urinary tract infection based on contaminated urinalyses may lead to antibiotic overuse and misdiagnosis of postoperative complications. Our results can help educate health care partners and discourage the use of clean-catch urine specimens when assessing women who have recently undergone vaginal surgery.
Hypoxia induces polycystin-1 expression in the renal epithelium
Authors: Grampp Steffen , Kraus Andre , Skoczynski Kathrin , Schiffer Mario , Krüger René , Naas Stephanie , Schödel Johannes , Buchholz Bjoern
Published: May 2023

Mutations in polycystin-1 which is encoded by the
PKD1
gene are the main causes for the development of autosomal dominant polycystic kidney disease. However, only little is known about the physiological function of polycystin-1 and even less about the regulation of its expression. Here, we show that expression of
PKD1
is induced by hypoxia and compounds that stabilize the hypoxia-inducible transcription factor (HIF) 1
α
in primary human tubular epithelial cells. Knockdown of HIF subunits confirms HIF-1α-dependent regulation of polycystin-1 expression. Furthermore, HIF ChIP-seq reveals that HIF interacts with a regulatory DNA element within the
PKD1
gene in renal tubule-derived cells. HIF-dependent expression of polycystin-1 can also be demonstrated
in vivo
in kidneys of mice treated with substances that stabilize HIF. Polycystin-1 and HIF-1
α
have been shown to promote epithelial branching during kidney development. In line with these findings, we show that expression of polycystin-1 within mouse embryonic ureteric bud branches is regulated by HIF. Our finding links expression of one of the main regulators of accurate renal development with the hypoxia signalling pathway and provides additional insight into the pathophysiology of polycystic kidney disease.
Compromising improves forecasting
Authors: Ferreiro Dardo N. , Deroy Ophelia , Bahrami Bahador
Published: May 2023

Predicting the future can bring enormous advantages. Across the ages, reliance on supernatural foreseeing was substituted by the opinion of expert forecasters, and now by collective intelligence approaches which draw on many non-expert forecasters. Yet all of these approaches continue to see individual forecasts as the key unit on which accuracy is determined. Here, we hypothesize that compromise forecasts, defined as the average prediction in a group, represent a better way to harness collective predictive intelligence. We test this by analysing 5 years of data from the Good Judgement Project and comparing the accuracy of individual versus compromise forecasts. Furthermore, given that an accurate forecast is only useful if timely, we analyze how the accuracy changes through time as the events approach. We found that compromise forecasts are more accurate, and that this advantage persists through time, though accuracy varies. Contrary to what was expected (i.e. a monotonous increase in forecasting accuracy as time passes), forecasting error for individuals and for team compromise starts its decline around two months prior to the event. Overall, we offer a method of aggregating forecasts to improve accuracy, which can be straightforwardly applied in noisy real-world settings.
The role of reservoir species in mediating plague's dynamic response to climate
Authors: Fell Henry Gillies , Jones Matthew , Atkinson Steve , Stenseth Nils Christian , Algar Adam C.
Published: May 2023

The distribution and transmission ofYersinia pestis, the bacterial agent of plague, responds dynamically to climate, both within wildlife reservoirs and human populations. The exact mechanisms mediating plague's response to climate are still poorly understood, particularly across large environmentally heterogeneous regions encompassing several reservoir species. A heterogeneous response to precipitation was observed in plague intensity across northern and southern China during the Third Pandemic. This has been attributed to the response of reservoir species in each region. We use environmental niche modelling and hindcasting methods to test the response of a broad range of reservoir species to precipitation. We find little support for the hypothesis that the response of reservoir species to precipitation mediated the impact of precipitation on plague intensity. We instead observed that precipitation variables were of limited importance in defining species niches and rarely showed the expected response to precipitation across northern and southern China. These findings do not suggest that precipitation–reservoir species dynamics never influence plague intensity but that instead, the response of reservoir species to precipitation across a single biome cannot be assumed and that limited numbers of reservoir species may have a disproportional impact upon plague intensity.
Regaining creativity in science: insights from conversation
Authors: Morgan Ruth M. , Kneebone Roger L. , Pyenson Nicholas D. , Sholts Sabrina B. , Houstoun Will , Butler Benjamin , Chesters Kevin
Published: May 2023

The ‘early modern’ (Renaissance) workshop was predicated on the idea that informal, open-ended cooperation enables participants to experience difference and develop new insights, which can lead to new ways of thinking and doing. This paper presents the insights that emerged from a conversation event that brought wide-ranging voices together from different domains in science, and across the arts and industry, to consider science leadership as we look to the future in a time of interlocking crises. The core theme identified was a need to regain creativity in science; in the methods of scientific endeavours, in the way science is produced and communicated, and in how science is experienced in society. Three key challenges for re-establishing a culture of creativity in science emerged: (i) how scientists communicate what science is and what it is for, (ii) what scientists value, and (iii) how scientists create and co-create science with and for society. Furthermore, the value of open-ended and ongoing conversation between different perspectives as a means of achieving this culture was identified and demonstrated.
Comparative microstructural study on the teeth of Mesozoic birds and non-avian dinosaurs
Authors: Wang Yan , Li Zhiheng , Wang Chun-Chieh , Bailleul Alida M. , Wang Min , O'Connor Jingmai , Li Jinhua , Zheng Xiaoting , Pei Rui , Teng Fangfang , Wang Xiaoli , Zhou Zhonghe
Published: May 2023

Although it is commonly considered that, in birds, there is a trend towards reduced dentition, teeth persisted in birds for 90 Ma and numerous macroscopic morphologies are observed. However, the extent to which the microstructure of bird teeth differs from other lineages is poorly understood. To explore the microstructural differences of the teeth of birds in comparison with closely related non-avialan dinosaurs, the enamel and dentine-related features were evaluated in four Mesozoic paravian species from the Yanliao and Jehol biotas. Different patterns of dentinal tubular tissues with mineralized extensions of the odontoblast processes were revealed through the examination of histological sectioning under electron microscopy. Secondary modification of the tubular structures, forming reactive sclerotic dentin of
Longipteryx
, and the mineralization of peritubular dentin of
Sapeornis
were observed in the mantle dentin region. The new observed features combined with other dentinal-associated ultrastructure suggest that the developmental mechanisms controlling dentin formation are quite plastic, permitting the evolution of unique morphologies associated with specialized feeding behaviours in the toothed birds. Proportionally greater functional stress placed on the stem bird teeth may have induced reactive dentin mineralization, which was observed more often within tubules of these taxa. This suggests modifications to the dentin to counteract potential failure.
Muscle Coordination Matters: Insights into Motor Planning using Corticospinal Responses during Functional Reaching
Authors: Augenstein Thomas E , Oh Seonga , Norris Trevor A , Mekler Joshua , Sethi Amit , Krishnan Chandramouli
Published: May 2023

The central nervous system (CNS) moves the human body by forming a plan in the primary motor cortex and then executing this plan by activating the relevant muscles. It is possible to study motor planning by using noninvasive brain stimulation techniques to stimulate the motor cortex prior to a movement and examine the evoked responses. Studying the motor planning process can reveal useful information about the CNS, but previous studies have generally been limited to single degree of freedom movements (e.g.,wrist flexion). It is currently unclear if findings in these studies generalize to multi-joint movements, which may be influenced by kinematic redundancy and muscle synergies. Here, our objective was to characterize motor planning in the cortex prior to a functional reach involving the upper extremity. We asked participants to reach for a cup placed in front of them when presented with a visual “Go Cue”.

Following the go cue, but prior to movement onset, we used transcranial magnetic stimulation (TMS) to stimulate the motor cortex and measured the changes in the magnitudes of evoked responses in several upper extremity muscles (MEPs). We varied each participant’s initial arm posture to examine the effect of muscle coordination on MEPs. Additionally, we varied the timing of the stimulation between the go cue and movement onset to examine the time course of changes in the MEPs. We found that the MEPs in all proximal (shoulder and elbow) muscles increased as the stimulation was delivered closer to movement onset, regardless of arm posture, but MEPs in the distal (wrist and finger) muscles were not facilitated or even inhibited. We also found that facilitation varied with arm posture in a manner that reflected the coordination of the subsequent reach. We believe that these findings provide useful insight into the way the CNS plans motor skills.
Neutrophils actively swell to potentiate rapid migration
Authors: Nagy Tamas L , Strickland Evelyn , Weiner Orion D.
Published: May 2023

While the involvement of actin polymerization in cell migration is well-established, much less is known about the role of transmembrane water flow in cell motility. Here, we investigate the role of water influx in a prototypical migrating cell, the neutrophil, which undergoes rapid, directed movement to sites of injury and infection. Chemoattractant exposure both increases cell volume and potentiates migration, but the causal link between these processes is not known. We combine single cell volume measurements and a genome-wide CRISPR screen to identify the regulators of chemoattractant-induced neutrophil swelling, including NHE1, AE2, PI3K-gamma, and CA2. Through NHE1 inhibition in primary human neutrophils, we show that cell swelling is both necessary and sufficient for the potentiation of migration following chemoattractant stimulation. Our data demonstrate that chemoattractant-driven cell swelling complements cytoskeletal rearrangements to enhance migration speed.
Functional network analysis identifies multiple virulence and antibiotic resistance systems inStenotrophomonas maltophilia
Authors: Pinto Larina , Shastry Rajesh P , Alva Shivakiran , Rao R. Shyama Prasad , Ghate Sudeep D
Published: May 2023

Stenotrophomonas maltophilia, an emerging multidrug-resistant opportunistic bacterium in humans is of major concern for immunocompromised individuals for causing pneumonia and bloodborne infections. This bacterial pathogen is associated with a considerable fatality/case ratio, with up to 100%, when presented as hemorrhagic fever. It is resistant to commonly used drugs as well as to antibiotic combinations. In-silico based functional network analysis is a key approach to get novel insights into virulence and resistance in pathogenic organisms. This study included the protein-protein interaction (PPI) network analysis of 150 specific genes identified for antibiotic resistance mechanism and virulence pathways. Eight proteins, namely,pilL,fliA,Smlt2260,Smlt2267,cheW,Smlt2318,cheZ, andfliMwere identified as hub proteins. Further docking studies of selected phytochemicals were performed against the identified hub proteins. Deoxytubulosine and Corosolic acid were found to be potent inhibitors of hub proteins of pathogenicS. maltophiliabased on protein-ligand interactive study. Further pharmacophore studies are warranted with these molecules to develop them as novel antibiotics againstS. maltophilia.
Growth and tension in explosive fruit
Authors: Mosca Gabriella , Eng Ryan , Adibi Milad , Yoshida Saiko , Lane Brendan , Bergheim Leona , Weber Gaby , Smith Richard S. , Hay Angela
Published: May 2023

Exploding seed pods of the common weedCardamine hirsutahave the remarkable ability to launch seeds far from the plant. The energy for this explosion comes from tension that builds up in the fruit valves. Above a critical threshold, the fruit fractures along its dehiscence zone and the two valves coil explosively, ejecting the seeds. Tension is commonly generated as seed pods dry, causing fruit tissues to deform. However, this does not happen inC. hirsuta.Instead, tension is produced by active contraction of growing exocarp cells in the outer layer of the fruit valves. Exactly how growth leads to contraction in these cells is unknown. Here we show that microtubule dynamics in the exocarp cell cortex control the specific orientation of cellulose microfibrils in the cell wall, and the consequent cellular growth pattern, which together drive contraction. We used mechanical modeling and simulations to show how tension emerges through the general process of plant cell growth, due to the highly anisotropic orientation of load-bearing cellulose microfibrils and their effect on cell shape. By explicitly defining the cell wall as multi-layered in our model, we discovered that a cross-lamellate pattern of cellulose microfibrils further enhances the developing tension in growing cells. Therefore, the interplay of cell wall properties with turgor-driven growth enables the fruit exocarp layer to develop sufficient tension to explode.
Natural variation of warm temperature-induced raffinose accumulation identifiesTREHALOSE-6-PHOSPHATE SYNTHASE 1as a modulator of thermotolerance
Authors: Reichelt Niklas , Korte Arthur , Krischke Markus , Mueller Martin J. , Maag Daniel
Published: May 2023

High temperature stress limits plant growth and reproduction. Exposure to high temperature, however, also elicits a conserved physiological response, which protects plants from the damage evoked by heat. This response involves a partial reconfiguration of the plant metabolome including the accumulation of the trisaccharide raffinose. In this study, we explored the intra-specific variation of warm temperature-induced raffinose accumulation as a metabolic marker for temperature responsiveness with the aim to identify genes that contribute to plant thermotolerance. By combining raffinose measurements in 250Arabidopsis thalianaaccessions following a mild heat treatment with genome-wide association studies we identified five genomic regions that were associated with the observed trait variation. Subsequent functional analyses confirmed a causal relationship betweenTREHALOSE-6-PHOSPHATE SYNTHASE 1(TPS1) and warm temperature-dependent raffinose synthesis. Moreover, complementation of thetps1-1null mutant with functionally distinct TPS1 isoforms differentially affected carbohydrate metabolism under more severe heat stress. While higher TPS1 activity was associated with reduced endogenous sucrose levels and thermotolerance, disruption of trehalose 6-phosphate signalling resulted in higher accumulation of transitory starch and sucrose and was associated with enhanced heat resistance. Taken together, our findings suggest a role of trehalose 6-phosphate in thermotolerance most likely through its regulatory function in carbon partitioning and sucrose homeostasis.
Prediction of peptide hormones using an ensemble of machine learning and similarity-based methods
Authors: Kaur Dashleen , Arora Akanksha , Vigneshwar Palani , Raghava Gajendra P.S.
Published: May 2023

Peptide hormones are genome-encoded signal transduction molecules released in multicellular organisms. The dysregulation of hormone release can cause multiple health problems and it is crucial to study these hormones for therapeutic purposes. To help the research community working in this field, we developed a prediction server that classifies hormonal peptides and non-hormonal peptides. The dataset used in this study was collected for both plants and animals from Hmrbase2 and PeptideAtlas databases. It comprises non-redundant 1174 hormonal and 1174 non-hormonal peptide sequences which were combined and divided into 80% training and 20% validation sets. We extracted a wide variety of compositional features from these sequences to develop various Machine Learning (ML) and Deep Learning (DL) models. The best performing model was logistic regression model trained on top 50 features which achieved an AUROC of 0.93. To enhance the performance of ML model, we applied Basic Local Alignment Search Tool (BLAST) to identify hormonal sequences using similarity among them, and motif search using Motif-Emerging and Classes-Identification (MERCI) to detect motifs present in hormonal and non-hormonal sequences. We combined our best performing classification model, i.e., logistic regression model with BLAST and MERCI to form a hybrid model that can predict hormonal peptide sequences accurately. The hybrid model is able to achieve an AUROC of 0.96, an accuracy of 89.79%, and an MCC of 0.8 on the validation set. This hybrid model has been incorporated on the publicly available website of HOPPred athttps://webs.iiitd.edu.in/raghava/hoppred/.
Human light meromyosin mutations linked to skeletal myopathies disrupt the coiled coil structure and myosin head sequestration
Authors: Carrington Glenn , Hau Abbi , Kosta Sarah , Dugdale Hannah F. , Muntoni Francesco , D’Amico Adele , Van den Bergh Peter , Romero Norma B. , Malfatti Edoardo , Vilchez Juan Jesus , Oldfors Anders , Pajusalu Sander , Õunap Katrin , Giralt-Pujol Marta , Zanoteli Edmar , Campbell Kenneth S. , Iwamoto Hiroyuki , Peckham Michelle , Ochala Julien
Published: May 2023

Myosin heavy chains encoded byMYH7andMYH2are among the most abundant proteins in human skeletal muscle. After decades of intense research using a wide range of biophysical and biological approaches, their functions have begun to be elucidated. Despite this, it remains unclear how mutations in these genes and resultant proteins disrupt myosin structure and function, inducing pathological states and skeletal myopathies termed myosinopathies. Here, we have analysed the effects of several commonMYH7andMYH2mutations located in light meromyosin (LMM) using a broad range of approaches. We determined the secondary structure and filament forming capabilities of expressed and purified LMM constructs in vitro, performedin-silicomodelling of LMM constructs, and evaluated the incorporation of eGFP-myosin heavy chain constructs into sarcomeres in cultured myotubes. Using muscle biopsies from patients, we applied Mant-ATP chase protocols to estimate the proportion of myosin heads that were super-relaxed, X-ray diffraction measurements to estimate myosin head order and myofibre mechanics to investigate contractile function. We found that humanMYH7andMYH2LMM mutations commonly disrupt myosin coiled-coil structure and packing of filamentsin vitro; decrease the myosin super-relaxed statein vivoand increase the basal myosin ATP consumption; but are not associated with myofibre contractile deficits. Altogether, these findings indicate that the structural remodelling resulting from LMM mutations induces a pathogenic state in which formation of shutdown heads is impaired, thus increasing myosin head ATP demand in the filaments, rather than affecting contractility. These key findings will help in the design of future therapies for myosinopathies.