bluuebunny/crossref_metadata_2025_split huggingface dataset:
A regulatory network involving calmodulin controls phytosulfokine peptide processing during drought-induced flower abscission
Authors: Wang Sai , Ge Siqi , Liu Xianfeng , Cheng Lina , Li Ruizhen , Liu Yang , Cai Yue , Meng Sida , Tan Changhua , Jiang Cai-Zhong , Qi Mingfang , Li Tianlai , Xu Tao 
Published: January 2025

Abstract
Drought stress substantially decreases crop yields by causing flowers and fruits to detach prematurely. However, the molecular mechanisms modulating organ abscission under drought stress remain unclear. Here, we show that expression of CALMODULIN2 (CaM2) is specifically and sharply increased in the pedicel abscission zone in response to drought and plays a positive role in drought-induced flower drop in tomato (Solanum lycopersicum). Due to partial functional redundancy with SlCaM6, we generated the Slcam2 Slcam6 double mutant, which showed minimal flower drop under drought. SlCaM2 and SlCaM6 interacted with the transcription factor signal responsive 3L (SlSR3L), with the 3 proteins operating in the same pathway, based on genetic data. We identified Protease inhibitor26 (SlPI26) as a target gene of SlSR3L by DNA affinity purification sequencing and transcriptome analysis. SlPI26 specifically inhibited the activity of the phytaspase SlPhyt2, hence preventing the generation of active phytosulfokine peptide and negatively regulating drought-induced flower drop. SlCaM2 and SlCaM6 enhanced the repression of SlPI26 expression by SlSR3L, promoting drought-induced flower drop. In addition, the nonphototropic hypocotyl3 (SlNPH3)–Cullin3 (SlCUL3) complex, which relies on auxin, interacted with SlSR3L to induce its degradation. However, under drought conditions, SlNPH3–SlCUL3 function is compromised due to lower auxin concentration. These results uncover a regulatory network that precisely controls floral drop in response to drought stress.
Challenges in the transition of care for rare connective tissue diseases: results from the 2023 ERN ReCONNET Transition of Care Task Force survey
Authors: Marrani Edoardo , Zajc Avramovic Mojca , Marinello Diana , Talarico Rosaria , Baldini Chiara , Collado-González Eva , Fonseca João Eurico , Schraven Linda , Oliveira Ramos Filipa , Triggianese Paola , Vissink Arjan , Mosca Marta , Avcin Tadej , Simonini Gabriele 
Published: January 2025

Abstract

Objectives
Two different European Reference Networks cover CTDs with paediatric onset, the European Reference Network on Rare and Complex Connective Tissue Diseases (ERN ReCONNET) and the European Reference Network on Rare Immunological Disorders (ERN RITA). The transition of care is a significant focus, with ReCONNET centres actively addressing this through updated programs. Despite these efforts, challenges persist. We aimed to inventory transitional care programs for rare CTDs across Europe.

Methods
In April 2023, the ERN ReCONNET Transition of Care Task Force, consisting of expert clinicians, patient advocates and coordination team members, created a survey to assess transitional care practices. The survey was distributed to ERN ReCONNET and ERN RITA centres and responses received by 15 March 2024 were analysed.

Results
A total of 67 responses from 59 centres across 20 European countries were collected. Paediatric rheumatologists typically initiated the transition process (49% of centres). Twenty centres had joint clinics. Despite positive self-assessments of transitional programs, significant limitations were noted. Transition policies varied, with only 40% of centres having a formal standardized policy and less than half of the centres adhering to available transition of care guidelines. Transfer readiness was evaluated using validated questionnaires in 13% of centres, while 29% transitioned patients based solely on age without any readiness assessments. The main challenges included finding adult-oriented centres and the lack of guidelines or engagement from adult centres. Adult healthcare providers also noted a lack of training in adolescent medicine.

Conclusion
The survey highlighted diverse transition practices and resources across centres, with challenges in readiness evaluation and the use of guidelines. Despite these obstacles, respondents rated ongoing transition processes positively. Enhancing patient perspectives in the transition process is crucial to meet their needs during this critical phase.
Skin of colour dermatology education in US primary care residency programmes: a nationwide cross-sectional survey of programme directors
Authors: LaMonica Lauren C , Hester Thomas , Thomas Reinie , Wang Frank 
Published: January 2025

Abstract

Background
Physicians-in-training report inadequate education in skin of colour (SOC) dermatology during residency. Although dermatology programmes have made progress in teaching SOC dermatology, the status of SOC dermatology education in primary care residency programmes remains unclear.

Objectives
To characterize SOC didactic and clinical training opportunities available to primary care residents, laying the groundwork for future curriculum development of SOC dermatology.

Methods
This cross-sectional study consisted of a nationwide 16-question survey disseminated by email between October 2022 and February 2023 to US primary care residency programmes identified using the Accreditation Council for Graduate Medical Education (ACGME) database.

Results
Of responding programmes (n = 49/1224, 4.0%), 29/49 offered SOC didactic training, most often through integration of content within general dermatology lectures (n = 29/49, 59.2%) and board review sessions (n = 13/49, 26.5%). Over half of programmes (n = 35/49, 71.4%) offered SOC clinical training through rotation in a general dermatology clinic (n = 33/49, 67.3%) and skin-related chief concerns in primary care clinics (n = 29/49, 59.2%). Programmes with directors indicating that they planned to incorporate SOC education into future curricula (n = 20/49, 40.8%) were more likely to already have SOC didactic and clinical training opportunities (P = 0.01 and P = 0.02, respectively). Regarding future directions, programme directors were most interested in integrating SOC topics within dermatology lectures (n = 31/49, 63.3%); identifying an expert (n = 31/49, 63.3%) and allocating lecture time (n = 10/49, 20.4%) were the most frequently cited barriers.

Conclusions
Some primary care programmes provide SOC dermatology didactic and clinical training opportunities, which are influenced by programme directors’ willingness to incorporate such training into curricula, and present opportunities for dermatologists to educate primary care residents.
Low‐intensity pulsed ultrasound enhances the osteogenic potential of PDLSCs‐derived extracellular vesicles through COMP/PI3K/AKT
Authors: Xiang Mingli , Guo Qiushuang , Liu Yulin , Zhang Gengchao , Liao Chengcheng , Xiao Linlin , Xiang Meiling , Long Sicen , Long Qian , Guan Xiaoyan , Liu Jianguo 
Published: January 2025

AbstractThe therapeutic potential of extracellular vesicles (EVs) in bone regeneration is noteworthy; however, their clinical application is impeded by low yield and limited efficacy. This study investigated the effect of low‐intensity pulsed ultrasound (LIPUS) on the therapeutic efficacy of EVs derived from periodontal ligament stem cells (PDLSCs) and preliminarily explored its mechanism. PDLSCs were cultured with osteogenic media and stimulated with or without LIPUS, and then EVs and LIPUS‐stimulated EVs (L‐EVs) were isolated separately. We investigated the biological characteristics and effects of these two EVs on cell proliferation, migration, osteogenic differentiation, and bone regeneration in vivo and in vitro, and explored the potential mechanism by analyzing protein profiles. LIPUS significantly stimulated the secretion of PDLSCs‐EVs, and L‐EVs exhibited stronger efficacy in promoting cell proliferation, migration, and osteogenic differentiation, thereby enhancing new bone formation. LIPUS stimulation affected the protein profile of PDLSCs‐EVs, and 42 proteins were upregulated and 4 proteins downregulated in L‐EVs when compared with EVs. LIPUS significantly upregulated the level of cartilage oligomeric matrix protein (COMP) in EVs, which enhanced EVs' osteogenic ability via the PI3K/AKT pathway. This study proposes that LIPUS has potential as an optimization method for enhancing the therapeutic effects of EVs in tissue regeneration.
Prolonged tamoxifen treatment induces iron deposition and ferroptosis in the liver
Authors: Yang Jianxin , Wang Dongyao , Wang Weili , Wu Chenghua , Li Chenqi , Shi Wenjing , Qian Jianxin , Xie Feng , Shen Hui , Tang Yuxiao 
Published: January 2025

AbstractTamoxifen is an inhibitor of estrogen receptors and was originally developed for breast cancer therapy. Besides, tamoxifen is widely used for Cre‐estrogen receptor‐mediated conditional knockout in transgenic mice. However, we found that the 3‐month feeding of 0.5 g/kg tamoxifen diet dramatically lowered the body weight of mice. The liver fat content and the serum lipid indicators were all decreased. But the liver injuries were identified, as illustrated by liver/body ratio and serum ALT and AST levels. The Sirius red staining and α‐SMA staining even showed fibrosis in the liver. The increased lipid peroxidation indicators MDA and LPO, and ferroptosis markers COX‐2, GPX4, SLC7A11, and ACSL4 implied the tamoxifen‐induced ferroptosis in the liver. We further found that tamoxifen induced hepatic iron deposition. The investigation of iron transporters found that tamoxifen upregulated ferric iron reductase STEAP3, ferrous iron transporter DMT1, and iron storage molecule ferritin, which were probably the reasons for tamoxifen‐induced iron deposition. The downregulation of the transferrin receptor and upregulation of hepcidin were more likely the responses to iron deposition. In conclusion, we found that tamoxifen disturbed the iron metabolism and induced liver injuries and ferroptosis, warranting attention to the applications of tamoxifen in cancer therapy and conditional gene knockout.
The Auditory Environment at Early Intervention Groups for Young Children With Hearing Loss: Signal to Noise Ratio, Background Noise, and Reverberation
Authors: Meijer Annerenée , Benard Michel Ruben , Woonink Aart , Başkent Deniz , Dirks Evelien 
Published: January 2025

Objectives:
One important aspect in facilitating language access for children with hearing loss (HL) is the auditory environment. An optimal auditory environment is characterized by high signal to noise ratios (SNRs), low background noise levels, and low reverberation times. In this study, the authors describe the auditory environment of early intervention groups specifically equipped for young children with HL.

Design:
Seven early intervention groups for children with HL were included in the study. A total of 26 young children (22 to 46 months) visiting those groups participated. Language Environmental Analysis recorders were used to record all sounds around a child during one group visit. The recordings were analyzed to estimate SNR levels and background noise levels during the intervention groups. The unoccupied noise levels and reverberation times were measured in the unoccupied room either directly before or after the group visit.

Results:
The average SNR encountered by the children in the intervention groups was +13 dB SNR. The detected speech of the attending professionals achieved the +15 dB SNR recommended by the American Speech-Language-Hearing Association in approximately 42% of the time. The unoccupied noise levels were between 29 and 39 dBA, complying with acoustic norms for classroom environments (≤35 dBA, by ANSI/ASA 12.60-2010 Part 1) for six out of seven groups. Reverberation time was between 0.3 and 0.6 sec for all groups, which complies to the acoustic norms for classroom environments for children without HL (0.6 or 0.7 sec, depending on the room size), while only one group complied to the stricter norm for children with HL (0.3 sec).

Conclusions:
The current findings show characteristics of the auditory environment of a setting that is specifically equipped and designed for groups of children with HL. Maintaining favorable SNRs seems to be the largest challenge to achieve within the constraints of an environment where young children gather, play, and learn. The results underscore the importance of staying attentive to keep spoken language accessible for children with HL in a group setting.
Synergistic effect of anemia and obstructive sleep apnea on hypertension: National Health and Nutrition Examination Survey 2015–2018
Authors: Yao Jiajia , He Xi , Wang Han , Wang Anzi , Zhen Lin 
Published: January 2025

Objective:
Anemia, obstructive sleep apnea (OSA), and hypertension are common social health problems. They are interconnected. This study assessed the independent association of anemia and OSA with hypertension and the interaction between anemia and OSA on hypertension in the US population.

Methods:
Data used by this retrospective study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2015–2018. The relative excess risk due to interaction (RERI), weighted logistic regression, and the attributable proportion due to interaction (AP) were used to investigate the interaction above. Its impact was also assessed via subgroup analysis by gender, age, race, diabetes, smoking, alcohol use, education, and marital status.

Results:
After covariate adjustment in 6949 eligible observers, it was found that compared with non-OSA patients, OSA patients were at higher risk of hypertension [odds ratio (OR) = 1.254, 95% confidence interval (CI) 1.099–1.432, P < 0.001). Meanwhile, OSA and anemia had a potential synergistic effect on the incidence of the disease (OR = 1.705, 95% CI: 1.390–2.091, P < 0.01): the RERI was 0.371, and the AP was 0.218. In addition, such effect was observed in the subgroup of other race (AP = 0.48), the nondrinking subgroup (AP = 2.50), the subgroup graduating from high school or above (AP = 0.28), the unmarried subgroup (AP = 0.4), the subgroup without diabetes (AP = 0.24), and the drinking subgroup (AP = 0.41).

Conclusion:
Anemia and OSA had a potential synergistic effect on hypertension. Their relationship needs to be further elucidated by a further study.
Mortality risks in different subtypes of masked hypertension in the Spanish ambulatory blood pressure monitoring registry
Authors: de la Sierra Alejandro , Ruilope Luis M. , Staplin Natalie , Stergiou George S. , Williams Bryan 
Published: January 2025

Objective:
We aimed to evaluate the risks of death and cardiovascular death of different subtypes of masked hypertension, defined by either isolated daytime or nighttime blood pressure (BP) elevation, or both, compared with patients with normal both office and 24-h BP.

Methods:
We selected 4999 patients with masked hypertension (normal office BP and elevated 24-h BP). They were divided in three different categories: isolated daytime masked hypertension (elevated daytime BP and normal nighttime BP, 800 patients), isolated nighttime masked hypertension (elevated nighttime BP and normal daytime BP, 1069 patients) and daytime and nighttime masked hypertension (elevation of both daytime and nighttime BP, 2989). All-cause and cardiovascular death (median follow-up 9.7 years) were assessed in each of these subtypes in comparison to 10 006 patients with normal both office and 24-h BP. Hazard ratios from Cox models after adjustment for clinical confounders were used for such comparisons.

Results:
Compared with patients with normal both office and 24-h BP, isolated daytime masked hypertension was not associated with an increased risk of death in models adjusted for clinical confounders [hazard ratio 1.07; 95% confidence interval (CI): 0.80–1.43]. In contrast, isolated nighttime masked hypertension (hazard ratio: 1.39; 95% CI 1.19–1.63) and daytime and nighttime masked hypertension (hazard ratio: 1.22; 95% CI 1.08–1.37) had an increased risk of death in comparison to patients with BP in the normal range. Similar results were observed for cardiovascular death.

Conclusion:
The risk of death in masked hypertension is not homogeneous and requires nocturnal BP elevation, either isolated or with daytime elevation. Isolated daytime masked hypertension is not associated with an increased risk of death.
Prevalence and correlates of uncontrolled hypertension and cardiovascular morbidity among patients with hypertension at the largest tertiary care hospital in Sri Lanka
Authors: Ranasinghe Priyanga , Manchanayake Minura , Perera Thilina , Liyanage Sandamini , Webb David J. 
Published: January 2025

Introduction:
Hypertension is the leading preventable cause of cardiovascular morbidity and mortality globally, with a disproportionate impact on low-income and middle-income countries like Sri Lanka. Effective blood pressure (BP) control improves outcomes in patients with hypertension. This study aimed to assess the prevalence of uncontrolled hypertension, and its correlates among Sri Lankan patients with hypertension in clinic settings.

Methods:
A cross-sectional study was done at the largest tertiary care hospital in Sri Lanka and patients with hypertension presenting to its medical clinics over a 6-month period were recruited. An interviewer-administered questionnaire captured sociodemographic, morbidity, and medication details from records. BP measurements were taken following standard guidelines with OMRON-X7 BP monitors. Multivariate logistic regression was used to identify significant associations (P < 0.05).

Results:
Among 600 patients (mean age 64 ± 9 years, 43% men), 55% had uncontrolled hypertension. Most (62%) were on 1 or 2 antihypertensives, primarily renin–angiotensin blockers (91%), with minimal (<10%) thiazide use. Uncontrolled hypertension was less common among furosemide (10.5%) and spironolactone (21.5%) users but frequent among those on alpha-blockers (16.3%). Coronary artery disease (58%), heart failure (9%), and stroke (17%) were more common in men and those with longstanding hypertension. Beta-blockers were favoured in those with cardiac comorbidities, and dihydropyridines in those with stroke. Potential treatment resistance, seen in 11%, was associated with increased cardiac morbidity, while sociodemographic factors and family history had no significant impact on BP control or cardiovascular morbidity.

Conclusion:
Uncontrolled hypertension and cardiovascular morbidity were highly prevalent. The data suggest the need for optimized antihypertensive regimens, with reduced use of alpha-blockers and early and prioritized incorporation of diuretics.
Minimum number of readings necessary for determining long-term visit-to-visit blood pressure variability to predict cardiovascular outcomes in people with diabetes
Authors: Kim Ju Hyeon , Oh Seungmi , Hong Soon Jun , Yu Cheol Woong , Joo Hyung Joon , Kim Yong Hyun , Kim Eung Ju 
Published: January 2025

Background:
People with diabetes often have increased blood pressure (BP) variability because of autonomic dysfunction and arterial stiffness, making it a critical factor in predicting clinical outcomes. We investigated the reproducibility of long-term visit-to-visit BP variability (VVV) and the minimum number of BP readings to reliably determine VVV in people with diabetes.

Methods:
This multicenter retrospective study used data from electronic health records of the Korea University Medical Center database. Altogether, 10 475 people with diabetes who had more than nine BP readings during a maximum period of 2 years were identified. This study focused on the coefficient of variation of these readings and their correlation with major adverse cardiovascular events (MACE) over a 3-year follow-up period.

Results:
The mean age of the participants was 65.2 years. Of these, 53.2% were men, and 87.4% had hypertension. The mean coefficient of variation of multiple SBP readings that best predicted the 3-year MACE were 8.4, 9.5, 9.0, 9.0, and 9.7 for three, five, seven, nine, and all readings, respectively. Patients with high VVV (coefficient of variation of five SBP readings >9) exhibited a higher incidence of 3-year MACE (10.1%) than those with low VVV (5.4%, P < 0.001). In the multivariable analysis, high VVV of both SBP and DBP were independently associated with 3-year MACE.

Conclusion:
Long-term VVV in the BP is a reproducible and reliable predictor of cardiovascular outcomes in people with diabetes. A minimum of five BP measurements are recommended for effective intraindividual VVV estimation and cardiovascular risk assessment.
Use of Hearing Aids Embedded with Inertial Sensors and Artificial Intelligence to Identify Patients at Risk for Falling
Authors: Steenerson Kristen K. , Griswold Bryn , Keating Donald P. , Srour Majd , Burwinkel Justin R. , Isanhart Erin , Ma Yifei , Fabry David A. , Bhowmik Achintya K. , Jackler Robert K. , Fitzgerald Matthew B. 
Published: January 2025

Objective
To compare fall risk scores of hearing aids embedded with inertial measurement units (IMU-HAs) and powered by artificial intelligence (AI) algorithms with scores by trained observers.

Study Design
Prospective, double-blinded, observational study of fall risk scores between trained observers and those of IMU-HAs.

Setting
Tertiary referral center.

Patients
Two hundred fifty participants aged 55–100 years who were at risk for falls.

Interventions
Fall risk was categorized using the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) test battery consisting of the 4-Stage Balance, Timed Up and Go (TUG), and 30-Second Chair Stand tests. Performance was scored using bilateral IMU-HAs and compared to scores by clinicians blinded to the hearing aid measures.

Main Outcome Measures
Fall risk categorizations based on 4-Stage Balance, Timed Up and Go (TUG), and 30-Second Chair Stand tests obtained from IMU-HAs and clinicians.

Results
Interrater reliability was excellent across all clinicians. The 4-Stage Balance and TUG showed no statistically significant differences between clinician and HAs. However, the IMU-HAs failed to record a response in 12% of TUG trials. For the 30-Second Chair Stand test, there was a significant difference of nearly one stand count, which would have altered fall risk classification in 21% of participants.

Conclusions
These results suggest that fall risk as determined by the STEADI tests was in most instances similar for IMU-HAs and trained observers; however, differences were observed in certain situations, suggesting improvements are needed in the algorithm to maximize accurate fall risk categorization.