bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic regulation of RNA splicing in human pancreatic islets
Authors: Atla Goutham , Bonàs-Guarch Silvia , Cuenca-Ardura Mirabai , Beucher Anthony , Crouch Daniel J. M. , Garcia-Hurtado Javier , Moran Ignasi ,   the T2DSystems Consortium, Cnop Miriam , Eliasson Lena , Esguerra Jonathan Lou S. , Eizirik Décio L. , Groop Leif , Jensen Thomas S. , Hansen Torben , Marchetti Piero , Mercader Josep M. , Mulder Hindrik , Stabile-Barnett Chris R. , Thirion Christian , Torrents David , Irimia Manuel , Prasad Rashmi B. , Gloyn Anna L. , Marselli Lorella , Suleiman Mara , Berney Thierry , de Koning Eelco J. P. , Kerr-Conte Julie , Pattou Francois , Todd John A. , Piemonti Lorenzo , Ferrer Jorge 
Published: September 2022

AbstractBackgroundNon-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown.ResultsWe examine splicing QTLs (sQTLs) in pancreatic islets from 399 human donors and observe that common genetic variation has a widespread influence on the splicing of genes with established roles in islet biology and diabetes. In parallel, we profile expression QTLs (eQTLs) and use transcriptome-wide association as well as genetic co-localization studies to assign islet sQTLs or eQTLs to T2D and T1D susceptibility signals, many of which lack candidate effector genes. This analysis reveals biologically plausible mechanisms, including the association of T2D with an sQTL that creates a nonsense isoform inERO1B, a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effector genes reveals overrepresented pathways, including regulators of G-protein-mediated cAMP production. The analysis of sQTLs also reveals candidate effector genes for T1D susceptibility such asDCLRE1B, a senescence regulator, and lncRNAMEG3.ConclusionsThese data expose widespread effects of common genetic variants on RNA splicing in pancreatic islets. The results support a role for splicing variation in diabetes susceptibility, and offer a new set of genetic targets with potential therapeutic benefit.
The maternal reduced uteroplacental perfusion model of preeclampsia induces sexually dimorphic metabolic responses in rat offspring
Authors: Hassanzadeh-Taheri Mohammadmehdi , Mohammadifard Mahtab , Erfanian Zahra , Hosseini Mehran 
Published: September 2022

Abstract
Background
Offspring born to preeclamptic mothers are prone to obesity, diabetes and hypertension in later life, but still, studies investigating the underlying mechanism are limited. Here, we aimed to investigate the impact of the reduced uteroplacental perfusion (RUPP) rat preeclampsia model on offspring metabolic outcomes.

Methods
Timed pregnant Wistar rats underwent RUPP or sham surgeries on day 14 of gestation. Glucometabolic parameters were evaluated on postnatal days (PND), 14 (childhood), and 60 (young adult). In addition, intraperitoneal glucose tolerance test (IPGTT), homeostatic model assessment of insulin resistance (HOMA-IR), immunohistochemical staining for insulin in pancreatic islets, arterial blood pressure and 24-h urine protein (24hUP) excretion were performed at PND60.

Results
Male, but not female, young adult rats (PND60) of RUPP dams exhibited an impaired IPGTT, decreased circulatory insulin and weakened pancreatic insulin immunoreactivity. Compared to the male offspring of the sham group, the body mass of male RUPP offspring significantly caught up after PND42, but it was not sex-specific. RUPP pups also exhibited upregulations in glucagon (only males) and ghrelin (both sexes with a more significant increase in males) during PND14–PND60. However, in sham offspring (both sexes), glucagon levels were downregulated and ghrelin levels unchanged during PND14–PND60. The blood pressure, HOMA-IR and 24hUP values did not alter in RUPP pups.

Conclusions
The overall results suggest that maternal RUPP has negative and sex-specific impacts on insulin, glucagon and ghrelin regulations in offspring and that, as young adults, male RUPP rats may be more prone to develop obesity and diabetes.
The glutamate metabotropic receptor 5 (GRM5) gene is associated with beef cattle home range and movement tortuosity
Authors: Moreno García Cristian A. , Zhou Huitong , Altimira David , Dynes Robyn , Gregorini Pablo , Jayathunga Sadeepa , Maxwell Thomas M. R. , Hickford Jonathan 
Published: September 2022

AbstractBackgroundThe grazing behaviour of herbivores and their grazing personalities might in part be determined genetically, but there are few studies in beef cattle illustrating this. In this study, we investigated for first time the genetic variation within a candidate ‘grazing gene’, the glutamate metabotropic receptor 5 gene (GRM5), and tested associations between variation in that gene and variation in grazing personality behaviours (GP-behaviours) displayed by free-ranging cows during winter grazing in the steep and rugged rangelands of New Zealand. Mature beef cows (n = 303, from 3 to 10 years of age) were tracked with global positioning system (GPS) and, with 5-minutes (min) relocation frequency, various GP-behaviours were calculated. These included horizontal and vertical distances travelled, mean elevation, elevation range, elevation gain, slope, home range and movement tortuosity, variously calculated using daily relocation trajectories with repeated measurements (i.e., 7 to 24 days (d)) and satellite-derived digital elevation models (DEM). The different GP-behaviours were fitted into mixed models to ascertain their associations with variant sequences and genotypes ofGRM5.ResultsWe discovered threeGRM5variants (A, BandC)and identified the six possible genotypes in the cattle studied. The mixed models revealed thatAwas significantly associated with elevation range, home range and movement tortuosity. Similarly,GRM5genotypes were associated (P < 0.05) to home range and movement tortuosity, while trends suggesting association (P <  0.1) were also revealed for elevation range and horizontal distance travelled. Most GP-behaviour models were improved by correcting for cow age-class as a fixed factor. The analysis of GP-behaviours averaged per cow age-class suggests that grazing personality is fully established as beef cows reached 4 years of age. Home range and movement tortuosity were not only associated withGRM5variation, but also negatively correlated with each other (r = − 0.27,P < 0.001).ConclusionsThere seems to be a genetically determined trade-off between home range and movement tortuosity that may be useful in beef cattle breeding programmes aiming to improve the grazing distribution and utilisation of steep and rugged rangelands.
Global Englishes and translanguaging in textbook design and curriculum development for universities in the Greater Bay Area of China
Authors: Fang Fan , Yuan Limin , Xu Hongchen , Wang Xueyi 
Published: September 2022

AbstractThe development of English as a global language has urged the field of Teaching English to Speakers of Other Languages (TESOL) to implement some reforms in relation to textbook design and curriculum development as well as the approaches to and goals of English language teaching (ELT). From the multilingual perspective, Global Englishes (GE) and translanguaging have both challenged the traditional native-oriented goal of ELT. Based on the level of language policy planning in the multilingual Greater Bay Area of China, this paper addresses the need to incorporate GE and translanguaging into textbook design and curriculum development. Referring to Byram’s framework of cultural content in textbooks, and to the GE proposal of exposure of multilingualism/multiculturalism and respect of diverse culture and identity in ELT, the paper further reports a case study to analyse the cultural content of the textbook,Speaking Critically: Intercultural Conversation. The paper also explores university students’ attitudes towards the integration of Chinese local culture into textbooks. The paper ends by addressing some challenges associated with translating GE and translanguaging into textbook design and curriculum development, and it provides further implications of such a proposal.
Genomic Classification of HER2-Positive Patients With 80-Gene and 70-Gene Signatures Identifies Diversity in Clinical Outcomes With HER2-Targeted Neoadjuvant Therapy
Authors: Whitworth Pat W. , Beitsch Peter D. , Murray Mary K. , Richards Paul D. , Mislowsky Angela , Dul Carrie L. , Pellicane James V. , Baron Paul L. , Rahman Rakhshanda Layeequr , Lee Laura A. , Dupree Beth B. , Kelemen Pond R. , Ashikari Andrew Y. , Budway Raye J. , Lopez-Penalver Cristina , Dooley William , Wang Shiyu , Dauer Patricia , Menicucci Andrea R. , Yoder Erin B. , Finn Christine , Blumencranz Lisa E. , Audeh William 
Published: September 2022

PURPOSE The prospective Neoadjuvant Breast Registry Symphony Trial compared the 80-gene molecular subtyping signature with clinical assessment by immunohistochemistry and/or fluorescence in situ hybridization in predicting pathologic complete response (pCR) and 5-year outcomes in patients with early-stage breast cancer. METHODS Standard-of-care neoadjuvant chemotherapy combined with trastuzumab or trastuzumab plus pertuzumab was given to patients with human epidermal growth factor receptor 2 (HER2)–positive tumors (n = 295). pCR was the primary end point, with secondary end points of distant metastasis-free survival and overall survival at 5 years. RESULTS Among clinically defined HER2-positive (cHER2) tumors, the 80-gene assay identified 29.5% (87 of 295) as Luminal-Type (cHER2/gLuminal), 14.9% (44 of 295) as Basal-Type (cHER2/gBasal), and 55.6% (164 of 295) as HER2-Type (cHER2/genomically classified as HER2 [gHER2]). Patients with cHER2/gHER2 tumors had a higher pCR rate (61.6%) compared with non-gHER2 tumors (26.7%; P < .001). Dual targeting for cHER2/gHER2 tumors yielded a higher pCR rate (75%) compared with those treated with single HER2-targeted therapy (54%; P = .006). For cHER2/gBasal tumors, the 42.9% pCR rate observed with dual targeting was not different from that with trastuzumab alone (46.4%; P = .830). Among those with cHER2/gBasal tumors, 5-year distant metastasis-free survival (68.6%; 95% CI, 49.1 to 81.9) was significantly worse than in patients with cHER2/gLuminal tumors (88.9%; 95% CI, 78.0 to 94.6) and cHER2/gHER2 tumors (87.4%; 95% CI, 80.2 to 92.2; P = .010), with similar corresponding overall survival differences. CONCLUSION The 80-gene assay identified meaningful genomic diversity in patients with cHER2 disease. Patients with cHER2/gHER2 tumors, who benefitted most from dual HER2-targeted therapy, accounted for approximately half of the cHER2 cohort. Genomically Luminal tumors had low pCR rates but good 5-year outcomes. cHER2/gBasal tumors derived no benefit from dual therapy and had significantly worse 5-year prognosis; these patients merit special consideration in future trials.
New Horizons: Emerging Antidiabetic Medications
Authors: Mingrone Geltrude , Castagneto-Gissey Lidia , Bornstein Stefan R 
Published: September 2022

Abstract
Over the past century, since the discovery of insulin, the therapeutic offer for diabetes has grown exponentially, in particular for type 2 diabetes (T2D). However, the drugs in the diabetes pipeline are even more promising because of their impressive antihyperglycemic effects coupled with remarkable weight loss.
An ideal medication for T2D should target not only hyperglycemia but also insulin resistance and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the new class of GLP1 and gastric inhibitory polypeptide dual RAs counteract 2 of these metabolic defects of T2D, hyperglycemia and obesity, with stunning results that are similar to the effects of metabolic surgery.
An important role of antidiabetic medications is to reduce the risk and improve the outcome of cardiovascular diseases, including coronary artery disease and heart failure with reduced or preserved ejection fraction, as well as diabetic nephropathy, as shown by SGLT2 inhibitors.
This review summarizes the main drugs currently under development for the treatment of type 1 diabetes and T2D, highlighting their strengths and side effects.
Approach to the Patient With Congenital Hypothyroidism
Authors: Stoupa Athanasia , Kariyawasam Dulanjalee , Nguyen Quoc Adrien , Polak Michel , Carré Aurore 
Published: September 2022

Abstract
Congenital hypothyroidism (CH) is the most frequent neonatal endocrine disorder and the most common preventable cause of development delay and growth failure if diagnosed and treated early. The thyroid is the first endocrine gland to develop during embryonic life and to be recognizable in humans. Thyroid development and maturation can be divided into 2 phases: a first phase of embryogenesis and a second phase of folliculogenesis and differentiation with thyroid hormone production at the final steps. Regulation of the thyroid function requires normal development of the hypothalamic–pituitary–thyroid axis, which occurs during the embryonic and neonatal period. Defects in any of steps of thyroid development, differentiation, and regulation lead to permanent CH. Newborn screening programs, established in only one-third of countries worldwide, detect CH and are cost-effective and highly sensitive and specific. During the last decade, epidemiology of CH has changed with increased frequency of thyroid in situ in primary CH. Advances in molecular testing have expanded knowledge and understanding of thyroid development and function. However, a molecular cause is identified in only 5% of CH due to thyroid dysgenesis. The purpose of this article is to describe the clinical approach to the child with CH, focusing on diagnostic work-up and future challenges on optimizing thyroid replacement therapy and regenerative medicine. The review is written from the perspective of the case of 2 girls referred for CH after newborn screening and diagnosed with thyroid ectopy. The genetic work-up revealed novel mutations in TUBB1 gene, associated with large platelets and abnormal platelet physiology.
Acute Hiccups Detected by Electromyographic Recordings During Resection of a Vestibular Schwannoma
Authors: Niedermeyer Sebastian , Greve Tobias , Lamm Ludwig-Maximilian , Thorsteinsdottir Jun , Schichor Christian , Tonn Joerg-Christian , Szelényi Andrea 
Published: September 2022

BACKGROUND AND IMPORTANCE:
Intraoperative neuromonitoring (IONM) is routinely used to monitor cranial nerve function during resection of vestibular schwannomas. Sudden movements in the surgical field can be a disturbing factor for the surgeon. IONM can help determine the cause of unexpected patient movements.

CLINICAL PRESENTATION:
We report the case of a 54-year-old patient who underwent retromastoid craniotomy and resection of a vestibular schwannoma. Toward the end of dissection of the tumor from the lower cranial nerves and brainstem, the patient showed repetitive shoulder elevation. Electroencephalography showed burst suppression, confirming deep sedation and excluding voluntary movements. Free-running electromyography recorded spontaneous, simultaneous, bilateral vocal cord activity that was synchronous with upper body movement. There was simultaneous but smaller activity in the right genioglossus muscle and levator veli palatini, indicative for far-field activity. These IONM findings allowed us to classify the clinical observations as intraoperative hiccups.

CONCLUSION:
Hiccups during general anesthesia are rare but should be considered as a differential diagnosis of sudden upper body movement. To the best of our knowledge, this is the first reported case of acute hiccups during resection of a vestibular schwannoma. IONM reliably distinguished it from an increase in intraoperative consciousness or accessory nerve activation resulting in shoulder movements.
Comparison between Eccentric-Only and Coupled Concentric–Eccentric Contractions for Neuromuscular Fatigue and Muscle Damage
Authors: RUAS CASSIO V. , LATELLA CHRISTOPHER , TAYLOR JANET L. , HAFF G. GREGORY , NOSAKA KAZUNORI 
Published: September 2022

ABSTRACT

Purpose
Eccentric contractions induce muscle damage, but less is known about the effects of preceding concentric contractions to eccentric contractions on muscle damage. We compared eccentric-only (ECC) and coupled concentric and eccentric contractions (CON–ECC) of the knee extensors for parameters of neuromuscular fatigue and muscle damage.

Methods
Twenty participants (age, 19–36 yr) were randomly placed into an ECC or a CON–ECC group (n = 10 per group), without significant (P > 0.06) differences in baseline neuromuscular variables between groups. The ECC group performed six sets of eight ECC at 80% of ECC one-repetition maximum (1-RMecc), whereas the CON–ECC group performed six sets of eight alternating concentric (CON) and ECC (16 contractions per set) at 80% of CON 1-RM and 1-RMecc, respectively. Maximal voluntary isometric contraction force, rate of force development, resting twitch force, maximal M-wave (MMAX), voluntary activation, motor evoked potentials, corticospinal silent period, short interval intracortical inhibition, and muscle soreness were measured before, immediately after, and 1–3 d after exercise.

Results
No significant (P ≥ 0.09) differences between ECC and CON–ECC were observed for changes in any variables after exercise. However, maximal voluntary isometric contraction force decreased immediately after exercise (ECC: −20.7% ± 12.8%, CON–ECC: −23.6% ± 23.3%) and was still reduced 3 d after exercise (ECC: −13.6% ± 13.4%, CON–ECC: −3.3% ± 21.2%). Rate of force development at 0–30 ms reduced immediately after exercise (ECC: −38.3% ± 33.9%, CON–ECC: −30.7% ± 38.3%). Voluntary activation, resting twitch force, and motor evoked potential/MMAX decreased and corticospinal silent period increased after exercise (all P ≤ 0.03), but short interval intracortical inhibition and MMAX did not change. Muscle soreness developed (P < 0.001) similarly for both groups (peak, 38.5 ± 29.5 mm).

Conclusions
CON–ECC did not exacerbate neuromuscular fatigue and muscle damage when compared with ECC, despite twice as many contractions performed. Thus, eccentric contractions (n = 48 in both groups) seemed to mainly mediate the neuromuscular responses observed.
Analysts’ Connections and M&A Outcomes
Authors: Cortes Felipe , Marcet Francisco 
Published: September 2022

This paper studies the role of shared analysts, who cover the target and the acquirer, in mergers and acquisitions outcomes. We find that deals where both firms are connected through shared analysts are less likely to be completed than deals without shared analysts. If completed, however, deals with shared analysts exhibit higher expected synergy gains, acquirer announcement returns, and acquirer post-completion performance. Shared analysts are also more likely to issue estimates about the acquirer in the proximity of the impending deal and their estimates are associated with a decrease in the uncertainty about acquirer’s cash flows. Our results highlight how the position of analysts in a deal results in an informational edge that enhances the screening of deals and mitigation of the acquirer’s informational disadvantage. Shared analysts who enhance the acquirer’s ability to screen out deals also exhibit superior career outcomes post-completion. We find similar results in the pre- and post-Regulation Fair Disclosure period, using brokerage house closures as a quasi-natural experiment and after controlling for analysts’ affiliations. This paper was accepted by Tomasz Piskorski, finance. Supplemental Material: The data files and online appendix are available at https://doi.org/10.1287/mnsc.2022.4468 .
Staff perspectives of a near-real time feedback intervention to improve patient experiences
Authors: Chessell Sarah , Courtiour Sandra , Colman Amanda , Porter Sam , Heaslip Vanessa 
Published: September 2022

Background/Aims Following several major reports of poor quality care in the NHS, including the Francis report, a multi-centre study was undertaken by to improve patient-centred care by implementing near-real time patient feedback. This article follows on from this and explores the experiences of staff from one hospital involved in the multi-centre study, including the learning from the intervention and how it affected their practice. Methods Semi-structured interviews were conducted with eight individuals who were involved in the original study, including five clinical staff members and three volunteers. Responses were transcribed and analysed thematically. Results The interviews highlighted four inter-related themes: the importance of communication; normalising feedback; confidence to talk to patients; and seeing from the patient perspective. Participants described how near real-time feedback enhanced communication, giving them confidence to interact with patients. Staff responded to negative patient feedback by making improvements to patient experiences. However, the initiative was not sustained following the conclusion of the study. Conclusions Near-real time patient feedback can be effective in improving staff–patient communication and creating a more positive experience for both patients and staff. However, this study highlights the need to examine the sustainability of improvement initiatives, as well as their initial effectiveness.
Community-level prevalence of epilepsy and of neurocysticercosis among people with epilepsy in the Balaka district of Malawi: A cross-sectional study
Authors: Keller Luise , Stelzle Dominik , Schmidt Veronika , Carabin Hélène , Reinhold Ann-Kristin , Keller Claudius , Welte Tamara M. , Richter Vivien , Amos Action , Boeckman Lindsay , Harrison Wendy , Winkler Andrea S. 
Published: September 2022

Background
Epilepsy and neurocysticercosis (NCC) prevalence estimates in sub-Saharan Africa are still scarce but show important variation due to the population studied and different screening and diagnosis strategies used. The aims of this study were to estimate the prevalence of epileptic seizures and epilepsy in the sampled population, and the proportion of NCC among people with epilepsy (PWE) in a large cross-sectional study in a rural district of southern Malawi.

Methods
We conducted a community-based door-to-door screening study for epileptic seizures in Balaka, Malawi between October and December 2012. Past epileptic seizures were reported through a 15-item questionnaire answered by at least one person per household generating five major criteria. People who screened positive were further examined by a neurologist to establish diagnosis. Patients diagnosed with epilepsy were examined and offered Taenia solium cyst antigen and antibody serological tests, and a CT scan for the diagnosis of NCC.

Results
In total, screening information on 69,595 individuals was obtained for lifetime occurrence of epileptic seizures. 3,100 (4.5%) participants screened positive, of whom 1,913 (62%) could be followed-up and underwent further assessment. Lifetime prevalence was 3.0% (95% Bayesian credible interval [CI] 2.8 to 3.1%) and 1.2% (95%BCI 0.9 to 1.6%) for epileptic seizures and epilepsy, respectively. NCC prevalence among PWE was estimated to be 4.4% (95%BCI 0.8 to 8.5%). A diagnosis of epilepsy was ultimately reached for 455 participants.

Conclusion
The results of this large community-based study contribute to the evaluation and understanding of the burden of epilepsy in the population and of NCC among PWE in sub-Saharan Africa.