bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Serum Testosterone and SHBG With Incident Fractures in Middle-aged to Older Men
Authors: Grahnemo Louise , Marriott Ross J , Murray Kevin , Tyack Lauren T , Nethander Maria , Matsumoto Alvin M , Orwoll Eric S , Vanderschueren Dirk , Yeap Bu B , Ohlsson Claes 
Published: October 2024

Abstract

Context
As men age, circulating testosterone (T) decreases, circulating SHBG increases, and the risk of fracture increases. It is unclear if circulating T, independently of comorbidities, is associated with fracture risk in men.

Objectives
To determine associations for T and SHBG with incident fractures in men.

Methods
We utilized the large (n = 205 973 participants, 11 088 any fracture cases, 1680 hip fracture cases, 1366 forearm fracture cases) and well-characterized UK Biobank cohort. Associations were modeled using Cox regressions, adjusting for multiple comorbidities/covariates, imputing for missing information, and assessing nonlinearity using cubic splines.

Results
For T, not considering SHBG, there was a nonlinear association with hip but not forearm fractures, with the lowest risk in the second quintile. However, in models adjusted for SHBG or using calculated free T, lower T was associated with a higher risk for fractures at all evaluated bone sites. Lower SHBG was strongly associated with a lower risk of hip and forearm fractures (Q1 vs Q5, hip 0.55, 0.47-0.65; forearm 0.62, 0.52-0.74).

Conclusion
Low circulating SHBG is strongly associated with a low risk of fracture at all evaluated bone sites, while the associations of circulating T with fracture risk are of lesser magnitude, nonlinear, inconsistent among fracture site, and affected by adjustment for SHBG. These findings demonstrate that circulating SHBG, rather than T, is a major independent biomarker of fracture risk in men. Consequently, both total T and SHBG should be assessed when examining the relationship of endogenous T concentrations with fractures in middle-aged to older men.
Endonuclease G is dispensable for sperm mitochondrial DNA elimination during spermatogenesis in mice
Authors: Xie Xuefeng , Li Jianshuang , Zhang Xue , Mo Shaomei , Li Ang , Sun Tian-Yi , Xie Feng-Yun , Luo Shi-Ming , Wang Guang , Ou Xiang-Hong , Sun Qing-Yuan , Zhou Qinghua 
Published: October 2024

ABSTRACT
Maternal inheritance of mitochondrial DNA (mtDNA) is a widespread phenomenon in eukaryotes. Our earlier research indicated that sperm mtDNA is removed prior to fertilization in mice, and Endonuclease G (ENDOG) orchestrates the degradation of sperm mitochondria in Caenorhabditis elegans. However, the mechanisms underlying sperm mtDNA disposal in mammals remain poorly understood. To investigate the potential role of ENDOG in sperm mtDNA elimination, we created Endog knockout (Endog−/−) mice. Our findings revealed that Endog−/− mice maintained normal spermatogenesis and fertility. Most strikingly, we detected no substantial discrepancy in sperm mtDNA copy number between Endog−/− and control mice. Furthermore, we noted that sperm mtDNA copy numbers were unchanged in both less motile and motile sperm isolated by Percoll gradient centrifugation from Endog−/− and control mice. Taken together, our results indicate that ENDOG is not essential for spermatogenesis or the elimination of sperm mtDNA in mice.
Hepatocyte differentiation requires anisotropic expansion of bile canaliculi
Authors: Bebelman Maarten P. , Belicova Lenka , Gralinska Elzbieta , Jumel Tobias , Lahree Aparajita , Sommer Sarah , Shevchenko Andrej , Zatsepin Timofei , Kalaidzidis Yannis , Vingron Martin , Zerial Marino 
Published: October 2024

ABSTRACT
During liver development, bipotential progenitor cells called hepatoblasts differentiate into hepatocytes or cholangiocytes. Hepatocyte differentiation is uniquely associated with multi-axial polarity, enabling the anisotropic expansion of apical lumina between adjacent cells and formation of a three-dimensional network of bile canaliculi. Cholangiocytes, the cells forming the bile ducts, exhibit the vectorial polarity characteristic of epithelial cells. Whether cell polarization feeds back on the gene regulatory pathways governing hepatoblast differentiation is unknown. Here, we used primary mouse hepatoblasts to investigate the contribution of anisotropic apical expansion to hepatocyte differentiation. Silencing of the small GTPase Rab35 caused isotropic lumen expansion and formation of multicellular cysts with the vectorial polarity of cholangiocytes. Gene expression profiling revealed that these cells express reduced levels of hepatocyte markers and upregulate genes associated with cholangiocyte identity. Timecourse RNA sequencing demonstrated that loss of lumen anisotropy precedes these transcriptional changes. Independent alterations in apical lumen morphology induced either by modulation of the subapical actomyosin cortex or by increased intraluminal pressure caused similar transcriptional changes. These findings suggest that cell polarity and lumen morphogenesis feed back to hepatoblast-to-hepatocyte differentiation.
Jag1 represses Notch activation in lateral supporting cells and inhibits an outer hair cell fate in the medial cochlea
Authors: de Haan Sandra , Corbat Agustin A. , Cederroth Christopher R. , Autrum Lisa G. , Hankeova Simona , Driver Elizabeth C. , Canlon Barbara , Kelley Matthew W. , Andersson Emma R. 
Published: October 2024

ABSTRACT
Notch signaling patterns the cochlear organ of Corti, and individuals with the JAG1/NOTCH2-related genetic disorder Alagille syndrome can thus experience hearing loss. We investigated the function of Jag1 in cochlear patterning and signaling using Jag1Ndr/Ndr mice, which are a model of Alagille syndrome. Jag1Ndr/Ndr mice exhibited expected vestibular and auditory deficits, a dose-dependent increase in ectopic inner hair cells, and a reduction in outer hair cells. Single cell RNA sequencing of the organ of Corti demonstrated a global dysregulation of genes associated with inner ear development and deafness. Analysis of individual cell types further revealed that Jag1 represses Notch activation in lateral supporting cells and demonstrated a function for Jag1 in gene regulation and development of outer hair cells. Surprisingly, ectopic ‘outer hair cell-like’ cells were present in the medial compartment and pillar cell region of Jag1Ndr/Ndr cochleae, yet they exhibited location-dependent expression of the inner hair cell fate-determinant Tbx2, suggesting Jag1 is required for Tbx2 to drive inner hair cell commitment. This study thus identifies new roles for Jag1 in supporting cells, and in outer hair cell specification and positioning.
Assessing the Risk of Postoperative Delirium Through Comprehensive Geriatric Assessment and Eastern Cooperative Oncology Group Performance Status of Elderly Patients With Gastric Cancer
Authors: Itami Takefumi , Yamamoto Kazuyoshi , Kurokawa Yukinori , Saito Takuro , Takahashi Tsuyoshi , Momose Kota , Yamashita Kotaro , Tanaka Koji , Makino Tomoki , Yasunobe Yukiko , Akasaka Hiroshi , Fujimoto Taku , Yamamoto Koichi , Nakajima Kiyokazu , Eguchi Hidetoshi , Doki Yuichiro 
Published: October 2024

Abstract
Background
Postoperative delirium is especially common and often problematic among elderly patients undergoing surgery. This study aimed to explore factors that can predict postoperative delirium in elderly patients undergoing gastric cancer surgery.

Methods
This cohort study included 255 patients age 75 years or older who underwent gastric cancer surgery between July 2010 and December 2020. All the patients underwent preoperative comprehensive geriatric assessment (CGA) evaluation by a geriatrician. In addition to the CGA items, this study investigated the association between postoperative delirium and clinicopathologic factors, including Eastern Cooperative Oncology Group performance status (ECOG-PS).

Results
The most common postoperative complication was delirium, present in 31 patients (12.2%). The group with delirium was significantly more likely to have ECOG-PS ≥ 2, diabetes mellitus, cardiovascular disease, or cerebral infarction. The CGA showed frailty in the Instrumental Activities of Daily Living scale (IADL), the Mini-Mental State Examination (MMSE), the Vitality Index (VI), and the Geriatric Depression Scale 15 (GDS-15). In the multivariate analysis, the independent risk factors for delirium were ECOG-PS ≥ 2 (P = 0.002) and MMSE-frailty (P < 0.001). Using an MMSE score of ≤ 23 and an ECOG-PS score of ≥ 2 as cutoffs, postoperative delirium was predicted with a sensitivity of 80.7% and a specificity of 74.1%.

Conclusion
Postoperative delirium might be more easily predicted based on the combination of MMSE and ECOG-PS for elderly patients with gastric cancer undergoing gastrectomy.
Pain Medication Data from the 2021 and 2022 National Football League Prescription Drug Monitoring Program
Authors: Hill Kevin P. , Kroenke Kurt , Wasserman Erin B. , Mack Christina , Ling Geoffrey S.F. , Mayer Thom , Solomon Gary S. , Sills Allen 
Published: October 2024

Abstract
We report 2021 and 2022 prescription drug monitoring program data that include pain medication prescriptions, including over-the-counter medications, issued to NFL players by either club physicians or external medical providers and entered in the NFL electronic medical record. Of 3142 players who signed a contract with at least one NFL Club during the 2021 season, there were 14,903 prescriptions for pain medications issued to 2207 players. During the 2022 season, there were 14,880 prescription pain medications issued to 2189 players (out of a population of 3152). Notably, most pain medication prescriptions across the two seasons were for nonsteroidal anti-inflammatory agents (NSAIDs; 85.1%), whereas only 2.9% were for opioids. Despite the demanding physical nature of professional football and the need for pain management during a season, the prevalence of opioid prescriptions among NFL players appears to be similar to and, in some cases, potentially lower than previous U.S. population-based data.
Co-infection of cytomegalovirus and Leishmania without splenomegaly resulting in immunosuppression in an HIV-negative patient
Authors: Bhatia Inder Preet Singh , Tripathi Siddharth , Singh Amulyajit , Hasvi Jayaraj , Rajan Amit , Tukaram Dahake Vandana 
Published: October 2024

Background: Leishmaniasis is caused by the parasite Leishmania donovani and transmitted by the bite of the sand fly vector Phlebotomus. This disease is endemic in the Bihar region of India. There are three common forms of the disease – cutaneous, mucosal and visceral leishmaniasis. The most common presentation of this disease is prolonged unexplained fever with hepatosplenomegaly. Case description: We report an unusual case of pyrexia of unknown origin (PUO) in a patient who was extensively worked up for PUO. She was found to have low CD4 counts even though serial samples were negative for HIV. Workup for PUO revealed a positive result for cytomegalovirus (CMV) IgM and polymerase chain reaction (PCR), fundoscopy suggestive of CMV retinitis and bone marrow biopsy suggestive of visceral leishmaniasis. Interestingly, there was no evidence of hepatosplenomegaly. She was diagnosed as a case of CMV infection and visceral leishmaniasis resulting in immunosuppression and was managed with parenteral ganciclovir followed by oral valganciclovir and amphotericin respectively. She had a dramatic response to the treatment and was discharged after two months of in hospital management. Conclusion: Co-infection of CMV and Leishmania in an immunocompromised patient with HIV-negative status without hepatosplenomegaly posed a diagnostic dilemma and is a rare presentation. This report shows the importance of diagnosis of this co-infectious state, which upon management with ganciclovir and amphotericin lead to resolution of symptoms and pancytopenia. Clinicians should be aware of the unusual presentation to avoid missing the diagnosis of this potentially life-threatening treatable condition.
‘Because I am a woman, an old woman, I have no voice’: gendered ageism and disempowerment of older women in three African countries
Authors: Roy Senjooti , Ayalon Liat , Veitch Georgina , Stovell Jemma 
Published: October 2024

Background and objectives:
Gendered ageism refers to the intersectionality of age and gender bias and discrimination. It is widely prevalent and leads to inequality, injustice, oppression, exploitation and disempowerment of older women. In this study, we explore the impacts of gendered ageism on three areas of older women’s lives in three African countries. These areas are: (1) participation in public and political life and access to justice and law enforcement; (2) family relations, inheritance, and land and property ownership; and (3) violence, abuse and neglect.

Research design and methods:
Eighteen women aged 54–85 years were interviewed for this study. Thematic analysis was undertaken to identify and explore disempowering impacts of gendered ageism on their lives and rights.

Results:
In all areas of the participants’ lives, their lack of voice in their inability to make choices, to claim their rights and to participate meaningfully in decision-making were highlighted. These manifested in the suppression of their interests, opinions and aspirations in public life; denial of justice; prejudice and discrimination within family settings; exploitation, harassment, abandonment and violence; and an overall devaluation, dehumanisation and silencing of older women.

Discussion:
Women often outlive men and experience marginalisation for a greater proportion of their lives. Yet, their lived experiences receive limited acknowledgement and redressal. In developing countries, older women face multiple forms of oppression arising from gendered ageism. This study highlights such experiences with the expectation that this will generate awareness, garner support from stakeholders and help inform policies for the protection and equal treatment of older women.
Multifunctional electrically switchable metalens
Authors: Wang Yu , Cui Dajian , Yang Guohui , Wang Yue , Wang Chunhui 
Published: October 2024

Here, we propose three all-solid-state, electrically switchable, transmissive, and
multifunctional metalens arrays comprising tunable metal-oxide
material BaTiO3 (BTO) nanopillars with different
structural parameters. To produce the required phase profile for each
metalens, the rectangular nanopillars, as the unit cell of the BTO
structure, are developed to support arbitrary combinations of two
independent phase shifts (0−2π) with bias voltage states of
0 V and 60 V, at first. Second, the structure parameters
of different functional metalens arrays are generated efficiently and
accurately based on the dual-phase modulation characteristics of a
single structure. Finally, we use the finite-difference time-domain
method to simulate the three kinds of switchable metalenses. The
results show that the three metalenses can realize the function of
adjustable focus position, switchable beam focusing and beam
deflection, and switchable beam focusing and beam splitting.
Characterization of heterodyne optical phase locking for relative laser frequency noise suppression in differential measurement
Authors: Kulur Ramamohan A. , Chua S. S. Y. , Zhang Y. , Yap M. J. , Wright J. , Holland N. A. , Forsyth P. W. F. , Slagmolen B. J. J. 
Published: October 2024

Laser frequency noise is particularly challenging to mitigate in low Fourier frequency measurement. For differential measurement schemes using heterodyne optical phase-locked loops, this noise can be common-mode suppressed in the final readout while maintaining a flexible frequency offset and a large frequency-shift dynamic range. We demonstrate simultaneous optical phase-locked loops using digital servo systems, with up to 300 MHz offset frequency range, 250 dB open-loop gain at 0.1 Hz, and control timescales suitable for low-frequency measurement. We also detail a four-laser differential measurement intended for use in a precision measurement device that uses optical phase-locked loops, suppressing relative free-running noise to reach below 0.1 Hz/Hz at 0.1 Hz in the measurement readout.
Community-Based Mycetoma Surveillance in Uganda: Identifying Knowledge Gaps and Training of Community Health Workers to Improve Case Detection
Authors: Kibone Winnie , Semulimi Andrew Weil , Kwizera Richard , Bongomin Felix 
Published: October 2024

Background
Mycetoma is an uncommon and neglected tropical disease in Uganda. We aimed to assess baseline knowledge and provide community health workers (CHWs) in Northern Uganda with knowledge to identify and refer presumptive mycetoma cases.

Methodology
Between March and August 2023, we conducted a concurrent triangulation mixed methods study among CHWs in Gulu and Pader districts on mycetoma. We conducted a 1 day in person training on mycetoma. Quantitative data were collected before (pretest), immediately (immediate posttest) and six months (6-month posttest) after the training and results compared using paired sample t test or one-way ANOVA. Qualitative data were collected using four focused group discussions, audio recorded, and analyzed using thematic content analysis.

Principal findings
Forty-five CHWs were enrolled, mostly male (66.7%, n = 30), with a median age of 36 years (IQR 29 43). Out of a total score of 18, the baseline mean knowledge score was 7±2.42, improving to 11±1.99 immediately posttest (p<0.001), and 10±2.35 at 6 months (p<0.001), without additional training. Significant knowledge improvements at 6 months were observed among female participants (p = 0.004), those aged 30 40 years (p = 0.031) or 40+ years (p = 0.035), and those with secondary education (p = 0.007). Over 6 months, CHWs screened 2,773 adults, identifying and referring 30 presumptive mycetoma cases. Qualitative findings revealed challenges and barriers to early identification and referral of mycetoma presumptive cases including limited knowledge, stigma, myths, lack of an indigenous name for mycetoma, delayed decision making, and transportation barriers.

Conclusions
This study highlights a significant knowledge gap among CHWs about mycetoma, with substantial improvement following training. The identification of presumptive cases by CHWs reflects their potential in community-based surveillance, emphasizing the need to integrate well-trained CHW to lead efforts for mycetoma surveillance and capacity building to enhance health outcomes in Uganda.
Mild burn amplifies the locomotive depression in demyelinated mice without muscle pathophysiological changes
Authors: Song Juquan , EI Ayadi Amina , Rontoyanni Victoria G. , Wolf Steven E. 
Published: October 2024

Introduction
Patients with mild burns take most accounts, however, the impact of mild burns is less known. Nerve destruction leads to muscle atrophy. We posit that even mild burn injury could worsen demyelinated nerves related to muscle pathophysiological impairment.

Methods
Young adult C57BL/6 (male, n = 60) mice were randomly fed with either a 0.2% cuprizone diet or a regular rodent diet for 4 weeks. At week 5, all mice were then grouped into mild scald burn with 10% TBSA and sham injury groups. Mice received animal behavior tests and in situ muscle isometric force measurement before euthanasia for tissue collection.

Results
Total horizontal ambulation and vertical activity were significantly reduced in mice with mild burn injury (p<0.05). Mice with the cuprizone diet had significantly less time to fall than those with the regular diet on day 7 after burn (p<0.05). No significant difference was found in gastrocnemius tissue weight among the groups, nor muscle isometric tensions (all p>0.05). The cuprizone diet increased the maximal phosphorylating respiration in mice muscle mitochondria (p<0.05). The muscle protein expressions of caspase 3, Fbx-32, and Murf1 significantly increased in mice with the cuprizone diet 3 days after burn (p<0.05). The signal expression of S100B significantly increased in mice with the cuprizone diet, and its expression was even greater on day 7 after burn injury. (p<0.05)

Conclusion
The cuprizone diet-induced locomotion and cognitive disorders were amplified by the mild burn injury in mice, which is associated with muscle intracellular signal alterations. However, mild burn injury does not cause mouse muscle weight loss and function impairment. The potential risk of pre-existed neural impairment could be aware when patients encounter even small or mild burns.
Prevalence and risk of occurrence of visible birth defects in mining areas in South Kivu: A hospital-based cross-sectional study
Authors: Cikomola Fabrice Gulimwentuga , Bisimwa Alliance Wani , Nyalundja Arsene Daniel , Barthélemy Ernest J. , Matabaro Bijoux Safi , Mukamba Franck Masumbuko , Nyamugabo Kinja , Alumeti Désiré Munyali , Kabesha Théophile , Miserez Marc , Sengeyi Dieudonné Mushengezi 
Published: October 2024

Background
Possible contamination related to mining activities might contribute with other risk factors in increasing the burden of birth defects (BDs) in many developing countries including the Democratic Republic of Congo. The subsequent prevalence is frequently underestimated. Implementation of focused public health interventions is hindered by the paucity of comprehensive data. We assessed the potential impact of mining on the prevalence and occurrence of visible BDs in neonates in South Kivu (SK).

Methods
A hospital-based cross-sectional study was conducted among 65,474 newborns registered in 7 hospitals in SK from 2016-2021. Hospitals were categorized based on mining activities in their respective catchment areas. Living in a mining zone was the exposure, whereas the outcome was visible BDs. Prevalence was estimated per 100,000 live births, and risk of occurrence with odds ratio (OR) and their 95% confidence interval.

Results
261 neonates with visible BDs were recorded accounting for a prevalence of 399 cases per 100,000 live births. The prevalence ranges between 217 and 1365 cases per 100,000 live births. An increased risk was found in mining zones(OR=2.07; 95%CI=1.59-2.68), Mubumbano(OR=1.72, 95%CI=1.22-2.43), and Mwenga(OR=3.89, 95%CI=2.73-5.54), whereas a reduced risk was reported in non-mining zones(OR=0.48, 95%CI=0.37-0.62) in Katana (OR=0.49, 95%CI=0.33-0.73). Musculoskeletal(28.74%) and central nervous systems(19.92%) were the most common BDs. A significant difference in prevalence for BDs involving the face, GI system and abdominal wall, musculoskeletal, central nervous and genitourinary systems between mining and non-mining zones was found(p<0.001).

Conclusion
There is an excessive risk for visible BDs in areas with hazardous mining activities in SK region.​​ More complex studies are needed to define the possible causal relationship. Moreover, findings generated herein should be corroborated by other research design, periodically monitored by public health authorities, and used to inform initiatives promoting enhanced environmental health, access to pediatric surgical care, and public health campaigns aimed at decreasing risk of BDs.