bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lats1 and Lats2 regulate YAP and TAZ activity to control the development of mouse Sertoli cells
Authors: Abou Nader Nour , Charrier Laureline , Meisnsohn Marie‐Charlotte , Banville Laurence , Deffrennes Bérengère , St‐Jean Guillaume , Boerboom Derek , Zamberlam Gustavo , Brind'Amour Julie , Pépin David , Boyer Alexandre 
Published: May 2024

AbstractRecent reports suggest that the Hippo signaling pathway regulates testis development, though its exact roles in Sertoli cell differentiation remain unknown. Here, we examined the functions of the main Hippo pathway kinases, large tumor suppressor homolog kinases 1 and 2 (Lats1 and Lats2) in developing mouse Sertoli cells. Conditional inactivation of Lats1/2 in Sertoli cells resulted in the disorganization and overgrowth of the testis cords, the induction of a testicular inflammatory response and germ cell apoptosis. Stimulated by retinoic acid 8 (STRA8) expression in germ cells additionally suggested that germ cells may have been preparing to enter meiosis prior to their loss. Gene expression analyses of the developing testes of conditional knockout animals further suggested impaired Sertoli cell differentiation, epithelial‐to‐mesenchymal transition, and the induction of a specific set of genes associated with Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ)‐mediated integrin signaling. Finally, the involvement of YAP/TAZ in Sertoli cell differentiation was confirmed by concomitantly inactivating Yap/Taz in Lats1/2 conditional knockout model, which resulted in a partial rescue of the testicular phenotypic changes. Taken together, these results identify Hippo signaling as a crucial pathway for Sertoli cell development and provide novel insight into Sertoli cell fate maintenance.
Handedness and Its Impact on a Career in Medicine
Authors: Sonnino Roberta E. , Sonnino Victor G. 
Published: May 2024

Abstract
Left-handedness in a world of right lateral bias can be an invisible barrier both in everyday life as well as in medical career development, and throughout a medical career. Common everyday life actions, including screwing in lightbulbs, inserting a screw, or any action that requires a clockwise rotation, is designed for “righties,” making life for “lefties” a challenge. Other examples include writing without a slant or without smudging. In medicine, the physical examination of a patient is taught using the right hand and standing on the right side of the patient, an awkward situation for left handers. Another major concern in medicine specifically, is handwriting—notoriously poor in lefties—impacting legibility in progress notes, prescriptions, and medical records. In surgery and other procedural specialties in particular, using instruments intended for right-handed individuals, including suturing and positioning at the operating room table, presents left-handed individuals with particular challenges. Left-handed medical students and residents are especially vulnerable, as they may feel uncomfortable requesting special accommodations for their “handedness.” The significance and impact of handedness often go unrecognized, yet may play a substantial role in career choices: the difficulties of being left-handed may dissuade students from pursuing their desired career. Solutions are available, including using instruments designed for left-handers (or learning to use “righty” instruments), and positioning at the operating room or procedure table as preferred by the left-handed individual. These solutions often require a cooperative attitude by colleagues. The authors describe the significance of handedness, including their own personal experiences, and offer some solutions for left-handed individuals who struggle to adapt to a right-handed world.
Nusinersen Initiation After Onset of Weakness Does Not Prevent Progression of Hip Instability
Authors: Kuong Evelyn Eugenie , Ip Hoi Ning Hayley , So Noah Lok Wah , To Michael Kai Tsun , Chow Wang , Wong Janus Siu Him , Chan Sophelia Hoi Shan 
Published: May 2024

Background:
We report changes in the natural history of hip instability with nusinersen treatment among patients with spinal muscular atrophy (SMA) type II after onset of weakness, historically wheelchair-bound but now potentially ambulatory in the era of disease-modifying therapy.

Methods:
Patients with genetically confirmed diagnoses of SMA type II who received intrathecal nusinersen from January 1, 2018, to June 30, 2022, were screened for inclusion. Patients with less than 6 months of follow-up, or prior hip surgeries were excluded. Primary clinical outcome measures included scores from Hammersmith motor functional scale expanded (HMFSE), revised upper limb module (RULM), 6-minute walk test (6MWT), and ambulatory status. Radiographic outcomes, including Reimer migration index, the presence of scoliosis, and pelvic obliquity, were also assessed. Secondary outcomes involved comparisons with a historical cohort of SMA type II patients treated at our institution who never received nusinersen.

Results:
Twenty hips from 5 boys and 5 girls were included in the analysis, with a mean follow-up of 3 years and 8 months. The median age at time of nusinersen initiation was 6.8 years old, ranging between 2.5 and 10.3 years. All patients developed lower limb motor weakness before nusinersen initiation. After treatment with nusinersen, 1 previously stable hip (5%) developed subluxation, 15 hips (75%) remain subluxated, 3 hips (15%) remain dislocated, and 1 hip (5%) remained stable, with a statistically significant difference between the pretreatment and posttreatment groups (P<0.01). Six patients (60%) were ambulatory at latest follow-up. Six patients (60%) had improved ambulatory ability; 2 had static ambulatory ability (20%); and 2 had deterioration in their walking ability. The median HFMSE score improved from 18.5 (range 0 to 46) to 22 (range 0 to 49) (P=0.813), whereas the median RULM score improved from 17 (range 2 to 28) to 21.5 (range 5 to 37), which was statistically significant (P=0.007).

Conclusions:
Hip instability persists despite treatment with nusinersen among patients with SMA type II who received nusinersen after onset of lower limb weakness.

Level of Evidence:
Therapeutic Level IV.
Outcomes of Ponseti Method for the Treatment of Clubfeet in Children With Arthrogryposis
Authors: Schaibley Claire , Torres-izquierdo Beltran , Hosseinzadeh Pooya 
Published: May 2024

Introduction:
The Ponseti serial casting method is the method of choice in treating children with congenital clubfeet. The arthrogrypotic clubfoot has traditionally been considered challenging to treat, with higher rates of recurrence and the need for more corrective surgeries. However, initial reports have found promising results in using the Ponseti method to treat arthrogrypotic feet. This study aims to compare the outcomes of idiopathic versus arthrogrypotic clubfeet following initial treatment with the Ponseti serial casting method.

Methods:
A retrospective review of medical records from a single institution was conducted. Data was collected from children ages 0 to 18 with idiopathic or arthrogrypotic clubfoot treated from 2002 to 2022 with Ponseti-style serial casting with a minimum 2-year follow-up. Recurrence was defined as the need for additional casting or subsequent surgeries following initial correction. Data was collected on relevant patient demographics, previous treatment, casting records, Achilles tenotomies, and surgical treatments.

Results:
A total of 352 patients (546 feet) met inclusion criteria. In all, 334 idiopathic and 18 arthrogrypotic patients were analyzed with an average follow-up duration of 3.4 and 4.2 years, respectively. Twelve patients had distal arthrogryposis, and 6 had amyoplasia. In all, 93.4% of idiopathic and 72.2% of arthrogrypotic patients successfully achieved correction with Ponseti casting and Achilles tenotomy. Recurrence rates were significantly higher in the arthrogrypotic group at 83.3% compared with 44.6% in the idiopathic group (P=0.001). A posterior or posterior medial release was performed in 35.0% of idiopathic and 66.7% arthrogrypotic feet.

Conclusions:
We report the largest series of arthrogrypotic clubfeet treated by Ponseti casting to the best of our knowledge. In contrast to earlier reports, our investigation underscores that while the Ponseti method may be able to secure initial correction in arthrogrypotic clubfeet, on average, at a 3-year follow-up, the prognosis is less favorable. These patients exhibit higher recurrence and often require operative treatment. Notably, a posterior medial release may eventually be needed in up to 6 of 10 patients.

Level of Evidence:
Level III—therapeutic studies—investigating the results of treatment.
Histological Assessment of the Effectiveness of Microneedling Device-Assisted Filler Delivery
Authors: Ugwu Nelson , Xun Helen , Dover Jeffrey S. , Boustany Ashley N. , Chung Hye Jin 
Published: May 2024

BACKGROUND
Microneedling is used to enhance transcutaneous drug delivery. However, the extent to which microneedling devices impact filler delivery and whether this varies by filler type, microneedling device type, and treatment sequence is not known.

OBJECTIVE
To histologically assess and quantify the delivery of commonly used fillers through microneedling, using both a microneedling pen and a microneedling roller. In addition, the authors investigated whether there is a variation in filler delivery based on the sequence of microneedling in relation to topical filler application.

METHODS
Ex vivo human abdominal skin samples were subjected to microneedling pen or microneedling roller treatment. Black tissue marking ink, hyaluronic acid, poly-l-lactic acid, or undiluted calcium hydroxyapatite was topically applied before or immediately after microneedling treatment.

RESULTS
Histological evaluation revealed a notable presence of black ink within channels formed by both microneedling treatments (15.5%–98.1%), whereas there was limited presence of the various filler types tested (0%–6.6%) in all settings. Topical application before microneedling treatment led to relatively higher filler/ink deposition within the channels formed by the microneedling treatments compared with topical application after microneedling.

CONCLUSION
Transcutaneous delivery of fillers was not significantly helped by microneedling treatment, whereas the microneedling devices demonstrated effective delivery of an aqueous solution.
P-selectin and C-reactive protein in relation to home blood pressure and coronary calcification: a SCAPIS substudy
Authors: af Geijerstam Peder , Rådholm Karin , Jonasson Lena , Lindahl Tomas L. , Engvall Jan , Nyström Fredrik H. , Alfredsson Joakim 
Published: May 2024

Background:
Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques.

Methods:
In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques.

Results:
Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4–61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40–1.98, P < 0.001] and hsCRP [OR 2.25, (95% CI 1.89–2.60), P < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72–3.10), P < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05–1.38), P = 0.007.

Conclusion:
Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.
Blood pressure variability assessed by office, home, and ambulatory measurements before and during antihypertensive drug treatment: a sub-analysis of the REVERENT randomized trial
Authors: Kyriakoulis Konstantinos G. , Kollias Anastasios , Bilo Grzegorz , Soranna Davide , Liu Chang-Yuan , Pengo Martino F. , Zambon Antonella , Zhang Wei , Destounis Antonios , Wang Ji-Guang , Stergiou George S. , Parati Gianfranco 
Published: May 2024

Objectives:
Blood pressure (BP) variability (BPV) can be assessed using office (OBP), home (HBP), or ambulatory BP (ABP) measurements. This analysis investigated the association and agreement between OBP, HBP, and ABP measurements for BPV assessment at baseline and 10 weeks after initiating antihypertensive drug therapy.

Methods:
Untreated hypertensive patients with elevated BPV were randomized to receive an angiotensin-converting enzyme inhibitor (ramipril) or a calcium channel blocker (nifedipine GITS) in a 10-week, open-label, blinded-end point study. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) (reading-to-reading analyses).

Results:
Data from 146 participants from three research centers (Athens/Greece; Milan/Italy; Shanghai/China) were analyzed [mean age 53 ± 10 (SD) years, male individuals 60%, baseline systolic OBP, HBP, and 24 h ABP 144 ± 9, 138 ± 10, and 143 ± 10 mmHg, respectively]. Post-treatment minus pre-treatment systolic CV difference was: OBP: 0.3%, P = 0.28; HBP: −0.2%, P = 0.20; 24 h ABP: 1.1%, P < 0.001. Home and ambulatory (not office) BPV indices presented weak-to-moderate correlation, both before and during treatment (range of coefficients 0.04–0.33). The correlation coefficient between systolic HBP and awake ABP CV was 0.21 and 0.28 before and during treatment, respectively (P < 0.05/< 0.001, respectively). Home and ambulatory (not office) BPV indices presented slight-to-fair agreement (range 64–73%) in detecting participants with high systolic BPV (top quartile of respective distributions) both before and during treatment (kappa range 0.04–0.27).

Conclusion:
These data showed a weak-to-moderate association between out-of-office (but not office) BPV indices both before and during BP-lowering treatment, with reasonable agreement in detecting individuals with high BPV. Out-of-office BP measurements provide more similar and consistent BPV information than office measurements.
TRPV1 signaling of perirenal adipose tissue promotes DOCA-Salt-induced hypertension and kidney injury
Authors: Hua Dongxu , Huang Wanlin , Huang Wen , Xie Qiyang , Tang Lu , Wu Xiaoguang , Gao Min , Xu Tianhua , Zhang Yue , Li Peng , Sun Wei , Kong Xiangqing 
Published: May 2024

Background:
Denervation of renal or perirenal adipose tissue (PRAT) can reduce arterial blood pressure in various hypertensive experimental models. Trpv1 (transient receptor potential vanillin 1) channel is highly expressed in the renal sensory nerves and the dorsal root ganglias (DRGs) projected by PRAT. However, it is currently unclear whether Trpv1 in DRGs projected from PRAT can regulate renal hypertension.

Methods:
We used resintoxin (RTX) to block the afferent sensory nerves of rat PRAT. We also constructed Trpv1-/- mice and Trpv1+/- mice or used the injection of AAV2-retro-shTrpv1 to detect the effects of Trpv1 knockout or knockdown of PRAT-projected DRGs on deoxycorticosterone acetate (DOCA)-Salt-induced hypertension and kidney injury.

Results:
Blocking the afferent sensory nerves of PRAT with RTX can alleviate DOCA-Salt-induced hypertension and renal injury in rats. And this blockade reduces the expression of Trpv1 in the DRGs projected by PRAT. Injecting AAV2-retro-shTrpv1 into the PRAT of DOCA-Salt mice also achieved the same therapeutic effect. However, DOCA-Salt-induced hypertension and renal injury can be treated in Trpv1+/- mice but not alleviated or even worsened in Trpv1-/- mice, possibly because of compensatory increase of Trpv5 in DRG of Trpv1-/- mice.

Conclusion:
Reducing, rather than eliminating, Trpv1 in DRG from PRAT-projection can reduce blood pressure and kidney damage in DOCA-Salt in rats or mice. Trpv1 in PRAT-DRGs may serve as a therapeutic target for salt-sensitive hypertension and its renal complications.
Visual assessment of Korotkoff sounds improves the accuracy of a validated professional automated auscultatory blood pressure monitor KOROT P3 Accurate
Authors: Menti Ariadni , Ntineri Angeliki , Kyriakoulis Konstantinos G. , Theodosiadi Aikaterini , Ntousopoulos Vasileios , Stathopoulou Panagiota , Kollias Anastasios , Stergiou George S. 
Published: May 2024

Objective:
A novel automated auscultatory upper-arm cuff blood pressure (BP) monitor for office use (KOROT P3 Accurate, previously InBody BPBIO480KV), which displays Korotkoff sound curves for each BP reading was recently developed. This study investigated whether the review of Korotkoff sound curves by healthcare professionals further improves the accuracy of the device by identifying unreliable BP readings.

Methods:
Three observers assessed independently the morphology of Korotkoff sound curves of BP measurements obtained during an ISO 81060-2:2018 validation study, and classified them as of good, fair, or poor quality (low amplitude or sound intensity, aberrant morphology, background noise, signal artifact, auscultatory gap, irregular rhythm). The observers were blinded to the study BP measurements.

Results:
Korotkoff sound curves of 255 BP readings obtained in 85 individuals were analyzed (mean age 57.3 ± 15.0 years, 53 men). Of the SBP readings 80.4/12.2/7.4% were classified as good/fair/poor, and DBP 76.9/12.2/10.9%. Inter-observer agreement in detecting poor-quality curves was 84.7/83.1% (systolic/diastolic). Of poor-quality curves, 10.5/60.7% (systolic/diastolic) clustered in the same individuals. The validation criterion 1 [mean test-reference BP difference ≤5 ± 8 (SD) mmHg] was satisfied for readings with good (0.1 ± 4.9/0.3 ± 3.8 mmHg, systolic/diastolic) and fair-quality curves (−0.4 ± 6.4/0.2 ± 5.0), but not for poor-quality ones (2.7 ± 8.8/3.6 ± 8.1). By excluding poor-quality readings (40 of 255), criterion 1 of the validation study was improved (0.2 ± 4.9/0.2 ± 3.9 versus 0.3 ± 5.5/0.6 ± 4.7 mmHg).

Conclusion:
The visual assessment of Korotkoff sounds generated during automated auscultatory BP measurement by the KOROT P3 Accurate professional monitor identifies unreliable readings and further improves the device accuracy.
Analgesic candidate adenosine A3 receptors are expressed by perineuronal peripheral macrophages in human dorsal root ganglion and spinal cord microglia
Authors: Sapio Matthew R. , Staedtler Ellen S. , King Diana M. , Maric Dragan , Jahanipour Jahandar , Ghetti Andre , Jacobson Kenneth A. , Mannes Andrew J. , Iadarola Michael J. 
Published: May 2024

Abstract
Adenosine receptors are a family of purinergic G protein–coupled receptors that are widely distributed in bodily organs and in the peripheral and central nervous systems. Recently, antihyperalgesic actions have been suggested for the adenosine A3 receptor, and its agonists have been proposed as new neuropathic pain treatments. We hypothesized that these receptors may be expressed in nociceptive primary afferent neurons. However, RNA sequencing across species, eg, rat, mouse, dog, and human, suggests that dorsal root ganglion (DRG) expression of ADORA3 is inconsistent. In rat and mouse, Adora3 shows very weak to no expression in DRG, whereas it is well expressed in human DRG. However, the cell types in human DRG that express ADORA3 have not been delineated. An examination of DRG cell types using in situ hybridization clearly detected ADORA3 transcripts in peripheral macrophages that are in close apposition to the neuronal perikarya but not in peripheral sensory neurons. By contrast, ADORA1 was found primarily in neurons, where it is broadly expressed at low levels. These results suggest that a more complex or indirect mechanism involving modulation of macrophage and/or microglial cells may underlie the potential analgesic action of adenosine A3 receptor agonism.
Monitoring lung recruitment
Authors: Cammarota Gianmaria , Vaschetto Rosanna , Vetrugno Luigi , Maggiore Salvatore M. 
Published: May 2024

Purpose of review
This review explores lung recruitment monitoring, covering techniques, challenges, and future perspectives.

Recent findings
Various methodologies, including respiratory system mechanics evaluation, arterial bold gases (ABGs) analysis, lung imaging, and esophageal pressure (Pes) measurement are employed to assess lung recruitment. In support to ABGs analysis, the assessment of respiratory mechanics with hysteresis and recruitment-to-inflation ratio has the potential to evaluate lung recruitment and enhance mechanical ventilation setting. Lung imaging tools, such as computed tomography scanning, lung ultrasound, and electrical impedance tomography (EIT) confirm their utility in following lung recruitment with the advantage of radiation-free and repeatable application at the bedside for sonography and EIT. Pes enables the assessment of dorsal lung tendency to collapse through end-expiratory transpulmonary pressure. Despite their value, these methodologies may require an elevated expertise in their application and data interpretation. However, the information obtained by these methods may be conveyed to build machine learning and artificial intelligence algorithms aimed at improving the clinical decision-making process.

Summary
Monitoring lung recruitment is a crucial component of managing patients with severe lung conditions, within the framework of a personalized ventilatory strategy. Although challenges persist, emerging technologies offer promise for a personalized approach to care in the future.