bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cooperative Gsx2–DNA binding requires DNA bending and a novel Gsx2 homeodomain interface
Authors: Webb Jordan A , Farrow Edward , Cain Brittany , Yuan Zhenyu , Yarawsky Alexander E , Schoch Emma , Gagliani Ellen K , Herr Andrew B , Gebelein Brian , Kovall Rhett A 
Published: June 2024

Abstract
The conserved Gsx homeodomain (HD) transcription factors specify neural cell fates in animals from flies to mammals. Like many HD proteins, Gsx factors bind A/T-rich DNA sequences prompting the following question: How do HD factors that bind similar DNA sequences in vitro regulate specific target genes in vivo? Prior studies revealed that Gsx factors bind DNA both as a monomer on individual A/T-rich sites and as a cooperative homodimer to two sites spaced precisely 7 bp apart. However, the mechanistic basis for Gsx–DNA binding and cooperativity is poorly understood. Here, we used biochemical, biophysical, structural and modeling approaches to (i) show that Gsx factors are monomers in solution and require DNA for cooperative complex formation, (ii) define the affinity and thermodynamic binding parameters of Gsx2/DNA interactions, (iii) solve a high-resolution monomer/DNA structure that reveals that Gsx2 induces a 20° bend in DNA, (iv) identify a Gsx2 protein–protein interface required for cooperative DNA binding and (v) determine that flexible spacer DNA sequences enhance Gsx2 cooperativity on dimer sites. Altogether, our results provide a mechanistic basis for understanding the protein and DNA structural determinants that underlie cooperative DNA binding by Gsx factors.
Line manager training and organizational approaches to supporting well-being
Authors: Dulal-Arthur T , Hassard J , Bourke J , Roper S , Wishart M , Belt V , Bartle C , Leka S , Pahl N , Thomson L , Blake H 
Published: June 2024

Abstract

Background
Employee mental health and well-being (MH&WB) is critical to the productivity and success of organizations. Training line managers (LMs) in mental health plays an important role in protecting and enhancing employee well-being, but its relationship with other MH&WB practices is under-researched.

Aims
To determine whether organizations offering LM training in mental health differ in the adoption of workplace- (i.e. primary/prevention-focused) and worker-directed (including both secondary/resiliency-focused and tertiary/remedial-focused) interventions to those organizations not offering LM training and to explore changes in the proportions of activities offered over time.

Methods
Secondary analysis of enterprise data from computer-assisted telephone interview surveys. The analysis included data from organizations in England across 4 years (2020: n = 1900; 2021: n = 1551; 2022: n = 1904; 2023: n = 1902).

Results
Offering LM training in mental health was associated with organizations’ uptake of primary-, secondary-, and tertiary-level MH&WB activities across all 4 years. The proportion of organizations offering primary-, secondary- and tertiary-level interventions increased over time. On average, tertiary-level activities were most adopted (2020: 80%; 2021: 81%; 2022: 84%; 2023: 84%), followed by primary-level activities (2020: 66%; 2021: 72%; 2022: 72%; 2023: 73%) and secondary-level activities (2020: 62%; 2021: 60%; 2022: 61%; 2023: 67%).

Conclusions
Offering LM training in mental health is associated with the adoption of other MH&WB practices by organizations. Suggesting that organizations that are committed to the mental health agenda are more likely to take a holistic approach (including both worker and workplace strategies) to promoting workforce mental health, rather than providing LM training in isolation.
Differential phosphorylation of Ca2+-permeable channel CYCLIC NUCLEOTIDE–GATED CHANNEL20 modulates calcium-mediated freezing tolerance in Arabidopsis
Authors: Peng Yue , Ming Yuhang , Jiang Bochen , Zhang Xiuyue , Fu Diyi , Lin Qihong , Zhang Xiaoyan , Wang Yi , Shi Yiting , Gong Zhizhong , Ding Yanglin , Yang Shuhua 
Published: June 2024

Abstract
Plants respond to cold stress at multiple levels, including increasing cytosolic calcium (Ca2+) influx and triggering the expression of cold-responsive genes. In this study, we show that the Ca2+-permeable channel CYCLIC NUCLEOTIDE–GATED CHANNEL20 (CNGC20) positively regulates freezing tolerance in Arabidopsis (Arabidopsis thaliana) by mediating cold-induced Ca2+ influx. Moreover, we demonstrate that the leucine-rich repeat receptor-like kinase PLANT PEPTIDE CONTAINING SULFATED TYROSINE1 RECEPTOR (PSY1R) is activated by cold, phosphorylating and enhancing the activity of CNGC20. The psy1r mutant exhibits decreased cold-evoked Ca2+ influx and freezing tolerance. Conversely, COLD-RESPONSIVE PROTEIN KINASE1 (CRPK1), a protein kinase that negatively regulates cold signaling, phosphorylates and facilitates the degradation of CNGC20 under prolonged periods of cold treatment, thereby attenuating freezing tolerance. This study thus identifies PSY1R and CRPK1 kinases that regulate CNGC20 activity and stability, respectively, thereby antagonistically modulating freezing tolerance in plants.
SUPPRESSOR OF FRIGIDA 4 cooperates with the histone methylation reader EBS to positively regulate root development
Authors: Huang Can , Wang Diao , Yang Yanqi , Yang Hong , Zhang Biaoming , Li Haitao , Zhang Haitao , Li Yan , Yuan Wenya 
Published: June 2024

Abstract
Maintenance and homeostasis of the quiescent center (QC) in Arabidopsis (Arabidopsis thaliana) root apical meristems are critical for stem cell organization and root development. Despite great progress in relevant research, the molecular mechanisms that determine the root stem cell fate and QC still need further exploration. In Arabidopsis, SUPPRESSOR OF FRIGIDA 4 (SUF4) encodes a C2H2-type zinc finger protein that represses flowering by transcriptional activation of FLOWERING LOCUS C (FLC) through the FRIGIDA (FRI) pathway, and EARLY BOLTING IN SHORT DAYS (EBS) is a bivalent histone reader that prevents premature flowering. Here, we found that SUF4 directly interacts with EBS in vivo and in vitro. Loss of function of SUF4 and/or EBS resulted in disorganization of the QC, aberrant cell division, and stunted root growth. RNA-seq and reverse transcription quantitative real-time polymerase chain reaction analysis revealed that SUF4 and EBS coregulate many root development-related genes. A series of biochemical analyses demonstrated that SUF4 directly binds to the promoter of SCARECROW (SCR), which encodes a key regulator of root development. Chromatin immunoprecipitation assay indicated that both SUF4 and EBS are recruited to the SCR locus in an interdependent manner to promote H3K4me3 levels and suppress H3K27me3 levels, thereby activating the expression of SCR. These findings improve our understanding of the function of SUF4 and EBS and provide insights into the molecular mechanism that couples a transcription factor and a histone methylation reader to modulate QC specification and root development in Arabidopsis.
The effect of experimentally induced sleep fragmentation and estradiol suppression on neurobehavioral performance and subjective sleepiness in premenopausal women
Authors: Grant Leilah K , Gonsalvez Irene , Cohn Aviva Y , Nathan Margo D , Harder Jessica A , Klerman Elizabeth B , Scheer Frank A J L , Kaiser Ursula B , Crawford Sybil , Luo Tianyu , Wiley Aleta , Rahman Shadab A , Joffe Hadine 
Published: June 2024

Abstract

Study Objectives
Menopause is associated with nighttime sleep fragmentation, declining estradiol, and impaired cognition. In a model of pharmacologically induced estradiol suppression mimicking menopause, we examined the impact of menopause-pattern sleep fragmentation on daytime neurobehavioral performance and sleepiness in premenopausal women.

Methods
Twenty premenopausal women completed two five-night inpatient studies in the mid-to-late follicular phase (estrogenized) and after pharmacological estradiol suppression (hypo-estrogenized). During each study, participants had an uninterrupted 8-hour sleep opportunity for two nights, followed by three nights where sleep was experimentally fragmented to mimic menopause-pattern sleep disturbance, and during which the sleep opportunity was extended to prevent shortening of the sleep duration. Neurobehavioral performance and subjective sleepiness were measured using the Psychomotor Vigilance Task and Karolinska Sleepiness Scale (KSS).

Results
Compared to unfragmented sleep, sleep fragmentation increased attentional lapses (+ 0.6 lapses, p &lt; .05), slowed reaction time (+ 9.4 milliseconds, p &lt; .01), and increased daytime sleepiness (+ 0.5 KSS score, p &lt; .001). Estradiol suppression increased attentional lapses (+ 0.8; p &lt; .001) and reaction time (+ 12.3, p &lt; .01) but did not significantly affect daytime sleepiness. The effect of sleep fragmentation on neurobehavioral performance differed by estradiol state, such that the adverse effects of sleep fragmentation on attentional lapses (+ 0.9, trend p = .06) and reaction time (+ 15, p &lt; .05) were observed only when estrogenized.

Conclusions
Menopause-pattern sleep fragmentation and estradiol suppression worsened neurobehavioral performance and daytime sleepiness, even while sleep duration was not reduced. The adverse effects of sleep fragmentation in the context of an adequate sleep duration highlight the importance of sleep continuity as a vital aspect of good sleep health.
Exploring the impact of gamification on engagement in a statistics classroom
Authors: Jack Eilidh , Alexander Craig , Jones Elinor M 
Published: June 2024

Abstract
In recent years, the integration of gamification into educational settings has garnered significant attention as a means to enhance student engagement and learning outcomes. By leveraging gamified elements such as points and leaderboards, educators aim to promote active participation, motivation and deeper understanding among students. This study investigates the effect of gamification on student engagement in a flipped statistics classroom environment. The findings suggest that gamification strategies, when effectively implemented, can have a positive impact on student motivation and engagement. This paper concludes with recommendations for educators, potential challenges such as superficial engagement and demotivation and future directions for research to address these challenges and further explore the potential of gamification in fostering student success.
Drug allergy awareness and perspectives with the implementation of the International Classification of Diseases-11
Authors: Tanno Luciana Kase , Briand Yann , Perie Alain , Castells Mariana , Demoly Pascal 
Published: June 2024

Purpose of reviewTo understand the current global scale of drug hypersensitivity (DH) and drug allergy (DA), and to identify possible strategies to increase the accuracy of epidemiological data.Recent findingsGlobal patterns of DH/DA seem to be changing and increasing worldwide, but there are still great challenges in capturing quality DH/DA mortality and morbidity statistics (MMS). DH/DA MMS may gain new perspectives with the global implementation of the International Classification of Diseases (ICD)-11. Improving the quality of epidemiological data related to DH/DA should clarify areas of uncertainty, which would lead to better strategies to reduce the burden of these conditions.SummaryDH/DA remains a complex and unaddressed problem globally that often deprives patients of optimal medication choices and places them at risk for life-threatening reactions. DH/DA labels should contribute to people well being, by protecting true allergic individuals from being re-exposed to their allergic drugs and providing needed medications to individuals wrongly labeled as allergic or who have lost allergic sensitivity. The true rate of DH/DA is in fact unknown due to a number of factors, such as misdiagnosis, miscoding and under- and over-notification, among others. Moreover, there is lack of data about DH/DA epidemiology in many countries. Difficulties on collecting accurate and comparable data should be acknowledged, with great impact in the correct labeling DH/DA in electronic health records and official statistics. More accurate definitions, classification and coding may contribute to a better-quality MMS thanks to the ICD-11, under implementation worldwide. Improving the quality of epidemiological data related to DH/DA should clarify areas of uncertainty, which would lead to better strategies to reduce the burden of these conditions. As knowledge derived from populations is key information for more realistic decision-making, the construction of the new section addressed to DH/DA in the ICD-11 will allow the collection of more accurate epidemiological data to support quality management of patients, and facilitate healthcare planning to implement public health measures to prevent and reduce the morbidity and mortality attributable to these conditions.
Patient Characteristics and Postoperative Outcomes of Surgically Treated Inferior Pole Patellar Sleeve Fractures
Authors: Desai Vineet M. , DeFrancesco Christopher J. , Yellin Joseph L. , Nguyen Jie C. , Williams Brendan A. 
Published: June 2024

Background:
Despite representing over half of all pediatric patella fractures, inferior pole patellar sleeve fractures (PSFs) are a relatively uncommon pediatric injury. As a result, existing literature on PSFs is limited to case reports and small case series. The purpose of this study was to evaluate the radiographic and clinical characteristics of operatively treated PSFs as well as outcomes following surgical management.

Methods:
A retrospective review of all inferior pole PSFs requiring surgery from 2007 to 2023 was performed at a single urban tertiary care children’s hospital. Cases were identified using diagnostic and billing codes. Patient demographics, injury characteristics, surgical techniques, and postoperative rehabilitation practices were recorded. Regional skeletal maturity, fracture characteristics, and postreduction patellar height were recorded. Postoperative complications were recorded and categorized using the modified Clavien-Dindo Classification System (CDS).

Results:
Thirty-eight inferior pole PSFs were identified meeting study criteria. The majority of patients were male (86.8%), and the mean age at injury was 11.0 years (range: 7.2 to 15.0). Mean BMI was 21.1. Radiographically, the majority of patients were Epiphyseal Fusion Stage 0 (nonunion), with a median postreduction Caton-Deschamps index (CDI) of 1.2 (IQR: 1.1 to 1.3). These fractures were predominantly treated with suture-based fixation (84%). Postoperative immobilization varied within the cohort, and the initiation of knee ROM was permitted at a median of 3.5 (IQR: 2.0 to 4.6) weeks. All patients regained full range of motion and straight leg raise without extensor lag, and return-to-sport was achieved by a median of 17.6 weeks (IQR: 12.8 to 30.3). Complications occurred in 10 (26.3%) patients, with 3 (7.9%) requiring a return to the OR (CDS Grade III).

Conclusions:
Inferior pole PSFs appear to occur most commonly among prepubertal males of normal BMI and normal patellar height. Despite variable rehabilitation protocols, operative management resulted in restoration of extensor mechanism function. Eight percent of patients experienced complications requiring unplanned surgery. This large series improves our understanding of the epidemiology, injury characteristics, and postoperative outcomes of an operatively treated cohort of a rare injury pattern.

Level of Evidence:
Level IV.
How to Prevent Nerve Root Injury in Uniportal Full Endoscopic Lumbar Fusion Surgery? Insights From a Cadaveric Anatomic Study With Simulation Surgery
Authors: Hsu Yu-Chia , Liu Yuan-Fu , Chang Chao-Jui , Hsiao Yu-Meng , Huang Yi-Hung , Liu Keng-Chang , Chen Chien-Min , Kim Hyeun-Sung , Lin Cheng-Li 
Published: June 2024

Study Design.
The study included 2 fresh-frozen cadavers.

Objective.
To elucidate the positional relationship between surgical instruments and nerve roots during full endoscopic facet-sparing (FE fs-TLIF) and full endoscopic facet-resecting (FE fr-TLIF) transforaminal lumbar interbody fusion and propose safe instrumentation insertion procedures and recommend cage glider designs aimed at protecting nerve roots.

Background.
Endoscopic surgical techniques are increasingly used for minimally invasive lumbar fusion surgery, with FE fr-TLIF and FE fs-TLIF being common approaches. However, the risk of nerve root injury remains a significant concern during these procedures.

Patients and Methods.
Eight experienced endoscopic spine surgeons performed uniportal FE fr-TLIF and FE fs-TLIF on cadaveric lumbar spines, totaling 16 surgeries. Postoperation, soft tissues were removed to assess the positional relationship between the cage entry point and nerve roots. Distances between the cage entry point, traversing nerve root, and exiting nerve root were measured. Safe instrumentation design and insertion procedures were determined.

Results.
In FE fr-TLIF, the mean distance between the cage entry point and traversing nerve root was significantly shorter compared with FE fs-TLIF (3.30 ± 1.35 vs. 8.58 ± 2.47 mm, respectively; P < 0.0001). Conversely, the mean distance between the cage entry point and the exiting nerve root was significantly shorter in FE fs-TLIF compared with FE fr-TLIF (3.73 ± 1.97 vs. 6.90 ± 1.36 mm, respectively; P < 0.0001). For FE fr-TLIF, prioritizing the protection of the traversing root using a 2-bevel tip cage glider was crucial. In contrast, for FE fs-TLIF, a single-bevel tip cage glider placed in the caudal location was recommended.

Conclusion.
This study elucidates the anatomic relationship between cage entry points and nerve roots in uniportal endoscopic lumbar fusion surgery. Protection strategies should prioritize the traversing root in FE fr-TLIF and the exiting root in FE fs-TLIF, with corresponding variations in surgical techniques.

Level of Evidence.
Level V.
Elite controllers microbiome: unraveling the mystery of association and causation
Authors: Bai Xiangning , Sönnerborg Anders , Nowak Piotr 
Published: June 2024

Purpose of review
To unravel the current knowledge and possible link between the gut microbiome and HIV-1 virological control in elite controllers (EC), who can suppress viral replication in the absence of antiretroviral therapy. In addition, to discuss the limitations of current research and propose future research directions.

Recent findings
EC possess a different gut bacterial microbiota profile in composition and functionality from that of treatment-naive HIV-1 viremic progressors (VP). Specifically, EC have a richer bacterial microbiota as compared to VP, which closely resembles the microbiota in HIV-1 negative healthy controls (HC). Differentially abundant bacteria are found between EC and VP or HC, though results vary among the few existing studies. These data imply that the gut microbiome could contribute to the natural suppression of HIV-1 infection.

Summary
An association between the gut microbiome and HIV-1 virological control is evidenced by recent studies. Yet, there are substantial knowledge gaps, and the underlying mechanism of how the microbiome influences the EC phenotype is far from clarified. Future research should consider diverse microbial communities, the complex microbe-host interactions, as well as yet-unidentified causal links between microbiome alterations and HIV-1 disease progression.
Sensitivity after Clitoral Reconstruction in Patients with Female Genital Mutilation
Authors: von Fritschen Uwe , Strunz Cornelia , Scherer Roland , Fricke Alba 
Published: June 2024

Background:
In the past decades, reconstructive choices after female genital mutilation extended beyond de-infibulation and scar release. The current trend to expand techniques addressing sexual and aesthetic aspects by reconstructing the clitoris and prepuce, and dissecting the clitoral nerves raises concern, as there is a paucity of evidence on the functional outcomes and suspected iatrogenic lacerations.

Methods:
A total of 128 female genital mutilation patients were included in the study. To evaluate clitoral sensitivity after elevation, the Semmes-Weinstein-monofilament test was performed before and after genital reconstruction.

Results:
Preoperatively, patients with a visually intact clitoris showed significantly better sensitivity compared with patients with a mutilated clitoris or infibulation (P < 0.0001). Surgery was performed in 84 patients. After clitoral reconstruction (CR), 70 of 73 patients were able to perceive 2.83 monofilaments (95.9%), whereas three perceived 3.61. Patients with a visually intact clitoris served as control, and 95.0% perceived 2.83 monofilaments. We showed a significant improvement of clitoral sensitivity (P = 0.0020) in the subgroup consisting of patients with a mutilated clitoris in whom the test was performed before and after reconstruction.

Conclusions:
Clitoral sensitivity improves significantly after CR. Seventy of 73 patients attained the same sensitivity as unharmed women. No patient showed a decreased sensitivity compared with their preoperative findings. Therefore, our study supports the argument that CR offers sufficient improvement of objective clitoral sensitivity without additionally addressing clitoral nerves.
Sex-Age Interplay Among Young Aged Egyptians With First Acute Myocardial Infarction
Authors: EL-Dosouky Ibtesam I. , El Seqelly Montaser M. , Ebrahiem Ahmed M. , Mohamed Mohamed Abdelhady 
Published: June 2024

Background:
The burden of modifiable risk factors in young Egyptian adults presenting with first acute myocardial infarction (AMI), sex differences, sex-age interplay, and its relationship with demographic, angiographic characteristics, and type of AMI is a good topic for discussion.

Methods:
The study enrolled 165 young (≤45 years old) consecutive, eligible patients diagnosed with first AMI (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction), for their demographic, angiographic, echocardiographic, and laboratory investigations and gender differences.

Results:
Our population were 29–45 years old and 12.1% were females, most of whom had ST-elevation myocardial infarction; obesity in females and smoking in males were the most prevalent; and the younger the age of females presenting with AMI the more aggressive underlying risk factors and the more reduction in left ventricular ejection fraction. Most of the female culprit lesions were thrombotic and the severity of atherosclerotic culprit lesions correlated positively with blood pressure.

Conclusions:
The age paradox in young females (regarding left ventricular ejection fraction and the traditional risk factors) and the thrombotic nature of the culprit lesion mandate early intensive 1-year and 2-year preventive strategies against coronary heart disease (CHD) with special concern for obesity as the main trigger early in life with proper control of blood pressure. In males, smoking cessation programs are the main target to ameliorate the progress of CHD hand in hand with the other 1-year and 2-year preventive strategies of CHD.