bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Letermovir for Cytomegalovirus Primary Prophylaxis on Myelosuppression and Immunosuppression in Lung Transplant Recipients
Authors: Kleiboeker Hanna L. , Prom Alyson , Paplaczyk Krista , Wang Jacob , Borkowski Nicole , Miner Brad , Wright Jennifer , Venkata Subramani Mrinalini , Arunachalam Ambalavanan , Betensley Alan D. , Tomic Rade , Myers Catherine N.
Published: November 2024

Background

Cytomegalovirus (CMV) is associated with detrimental outcomes after lung transplantation (LTX); primary prophylaxis (PPX) with valganciclovir (VGC) is guideline‐recommended. VGC is associated with myelosuppression, spurring interest in letermovir (LTV).

Methods

Adults undergoing LTX between January 1, 2021, and July 30, 2022 at our institution who were converted from VGC to LTV for PPX were evaluated. Outcomes included antimetabolite dosing during PPX, the incidence and frequency of myelosuppressive events, and the time to the first myelosuppressive event.

Results

Twenty‐nine LTX recipients met the inclusion criteria. Most patients received non‐lymphocyte‐depleting induction (96.6%) and had moderate risk CMV serostatus (D+/R+, 48.3%). Patients transitioned from VGC to LTV 177 days (IQR 102 days) post‐transplant. After conversion to LTV, patients tolerated higher daily doses of mycophenolate (721 mg vs. 1000 mg, p = 0.008) or azathioprine (33.3 mg vs. 62.5 mg, p = 0.478). The incidence of myelosuppressive events was reduced (100.0% vs. 62.1%, p < 0.001) including leukopenia (96.6% vs. 58.6%, p = 0.001), severe leukopenia (82.8% vs 31.0%, p < 0.001) and neutropenia requiring GCSF (96.6% vs. 48.3%, p < 0.001) while on VGC compared to LTV. While on LTV, patients had a reduced rate of myelosuppressive events compared to VGC (1 event per 6.2 patient days vs. 1 event per 14.7 patient days, p < 0.001). While on LTV, one patient had breakthrough viremia (3.4%) that was treated with (val)ganciclovir.

Conclusions

In this single‐center study, patients tolerated higher doses of antimetabolite immunosuppression, and the incidence and frequency of myelosuppressive events were reduced while on LTV compared to VGC. This evidence expands upon the current literature demonstrating improved tolerability of LTV in LTX recipients.
Outcomes of Hematopoietic Stem Cell Transplantation in Patients With Thalassemia Major: How Do Anti‐HLA Antibodies Impact?
Authors: Ersoy Gizem Zengin , Aksoy Basak Adakli , Erdem Melek , Karataş Lokman , Aydoğdu Selime , Öner Özlem Başoğlu , Dikme Gürcan , Bozkurt Ceyhun , Fışgın Tunç
Published: November 2024

Aim

To investigate the effects of anti‐human Leucocyte Antigen (HLA) antibody positivity on early hematopoietic stem cell transplantation (HSCT) results in patients with thalassemia major (TM).

Methods

One hundred and twenty‐four HLA‐matched HSCTs were performed in patients with TM between 2015 and 2022. Ninety‐one patients were screened for anti‐HLA antibodies by testing panel reactive antigens (PRA). Demographic and transplantation characteristics of patients were recorded. The presence of PRA was tested with the Antibody Testing Assay (Luminex LIFECODES HLA Antibody Identification System).

Results

The number of PRA‐positive patients was 54. There was no relationship between acute graft versus host disease (GVHD), chronic GVHD, grade of GVHD, and viral reactivation of the patients. However, platelet engraftment took around 3 days longer in the PRA‐positive group (p = 0.05). The median number of erythrocyte transfusions was significantly higher in PRA‐positive patients in the post‐transplant period (p = 0.003), as was the median number of platelet transfusions (p = 0.003). Treosulfan conditioning increased the stable mixed chimerism (MC) rate by 3.8‐fold (p = 0.011). In contrast, reduced rates of MC were found in patients who received matched unrelated donor cells or peripherally derived stem cells (p = 0.011 and p = 0.039, respectively) in the posttransplantation period in TM patients. PRA‐positivity did not affect MC (p = 0.478). However, 80% of patients who had primary graft failure (n = 5; p = 0.59) and 75% of patients who died (n = 4) were PRA positive (p = 0.64), but these results were statistically insignificant due to the low number of patients.

Conclusion

Anti‐HLA antibodies primarily delayed platelet engraftment in TM patients and increased the erythrocyte and thrombocyte transfusion requirements. Although PRA positivity was more common in patients with primary graft failure or who died, there was no statistically significant impact of PRA positivity on chimerism, acute or chronic GVHD, viral activation, or mortality rates.
Increasing stability of northern Austrian Lepidoptera populations over three decades
Authors: Ulrich Werner , Schmitt Thomas , Gros Patrick , Habel Jan Christian
Published: November 2024

Agricultural intensification has led to landscape homogenisation across major parts of Europe and to reduced diversity in flora and fauna. In Central Europe, the species composition of major insect groups is increasingly dominated by a few ecologically generalist and mobile species. So far, however, the degree of stability of population sizes in today's anthropogenic landscapes in comparison to the pre‐Anthropocene has hardly been analysed.

Here, we studied large museum records of Lepidoptera from northern Austria spanning the years 1990–2022 to infer trends in the stability of population sizes.

On average, population dynamics decreased and stability increased significantly over time. This trend was most pronounced in lowland regions, where agricultural intensification transformed the former heterogeneous landscapes into intensively managed grasslands and fields.

Community structures are now dominated by ubiquitous species. Habitat specialist species existing in isolated patches particularly decreased over time.

A metapopulation structure appeared to have a stabilising effect on population dynamics.

We conclude that reduced diversity and altered community composition might not only stem from selective population decline but also from altered patterns of population stochasticity. Higher population stability was associated with faunal homogenisation. Precise butterfly sensitivity analyses require long‐term data on average population sizes and on community composition.
Evaluation of Gemtuzumab Ozogamicin and Anthracycline Dosing for Favorable Risk Acute Myeloid Leukemia
Authors: Mort Joseph F. , Brighton David , DiBenedetto Samantha , Wells Leah , Clark Stephen M. , Reid Justin , Patel Imari , Jackson Clayton , Yelvington Bradley , Miller Ryan , Perciavalle Matthew , Walsh Katherine , Wolfe Heather , Locke Susan C. , Zeidner Joshua F. , Duong Vu H. , Reed Daniel R. , Dholaria Bhagirathbhai , LeBlanc Thomas W. , Keng Michael , Horton Bethany , El Chaer Firas
Published: November 2024

Gemtuzumab ozogamicin (GO) is a CD33‐targeting antibody‐drug conjugate approved for the treatment of CD33‐positive de novo and relapsed and refractory acute myeloid leukemia (AML). Subset analyses have demonstrated improved clinical outcomes in patients with favorable‐risk disease. It is unclear whether the addition of GO to cytarabine and anthracycline chemotherapy (7+3) improves clinical outcomes compared with other conventional regimens for AML. We evaluated the real‐world experience with GO added to 7+3 chemotherapy for patients with favorable risk AML. This retrospective analysis included 174 patients with de novo favorable risk AML undergoing induction chemotherapy between 2010 and 2020. The primary outcome was overall survival (OS) and secondary outcomes included rates of remission, measurable residual disease (MRD), and toxicity. Eighteen patients received GO, 37 received a high‐dose (HD) anthracycline, and 119 received an intermediate‐dose anthracycline. Composite complete remission was achieved in 162 patients (93.1%). Among the 54 patients who were assessed for MRD at remission, 66.7% were undetectable. An improvement in OS was seen for patients who received GO and those treated with HD anthracycline, which was better explained by differences in patient performance status and comorbidities. Patients who received GO did not show increased toxicity.
The rise and fall of Queckenstedt's test between 1916 and 1970, a milestone in spinal cord diagnostics and why it matters
Authors: Curt Armin , Zipser Carl Moritz
Published: November 2024

Background and purpose

In 1916, Hans H. G. Queckenstedt (1876–1918) was the first to describe a test aimed at detecting spinal cerebrospinal fluid (CSF) space obstruction through lumbar CSF pressure measurements in paraplegic patients. For this test, bilateral jugular vein compression was applied during lumbar puncture and consecutive changes in lumbar CSF pressure were then observed. Findings were rated as normal, or indicative of incomplete or complete spinal block. This test, known as Queckenstedt's test, became widely adopted and further developed in the field.

Methods

This systematic literature review provides an overview of the milestones in research using Queckenstedt's test.

Results

Clinical research involving Queckenstedt's test was widely disseminated across the globe. In 1922, the proof of concept for Queckenstedt's test was provided by James B. Ayer (1882–1963) through simultaneous cisternal and lumbar CSF pressure measurements. He found that the cisternal (in contrast to lumbar) pressure remained responsive in cases with spinal block. The test was further refined up until the 1960s, and was considered a routine diagnostic procedure for testing of spinal canal obstruction. Developments in non‐invasive spinal computed tomography and magnetic resonance imaging led to a significant decline in interest in Queckenstedt's test, and the test eventually disappeared from textbooks and clinical routine. However, at the beginning of the 21st century there was renewed interest in revealing the biomechanical properties of the CSF through advanced recording and computational techniques to complement spinal imaging.

Conclusion

Spine and spinal cord physicians should be familiar with Queckenstedt's test, which not only represented a milestone in spinal diagnostics, but provided a physiological framework for the appreciation of spinal cord compression that is still valid today.
Study on Structure Optimization and Vibration Fatigue Analysis of Aluminum and Composite Brake Control Boxes
Authors: Shangguan Yiming , Wang Wenjing , He Anrui , Wang Yuzhu , Zhu Jing
Published: November 2024

The brake control box beneath an EMU is exposed to dynamic and fluctuating load cases, increasing its susceptibility to vibration fatigue failure. A novel lightweight design approach was implemented to integrate structural and material optimizations. Static and fatigue tests of the T700/5429 CFRP were carried out to augment the stress analysis and predictions of the vibration fatigue life. The local stresses perpendicular and parallel to the welds were obtained to calculate the stress ratio, stress range, and allowable stress value corresponding to the stress component. The fatigue strength of the aluminum box was estimated on the basis of multiaxial criteria, and the fatigue life of the two boxes was predicted with Dirlik's theory. These computational findings unequivocally indicated a noteworthy reduction in damage to the composite box subsequent to lightweight modification, thereby successfully satisfying both the stiffness and strength criteria essential for the safety and reliability of the EMU.
Overlooked Vital Role of Persistent Algae‐Bacteria Interaction in Ocean Recalcitrant Carbon Sequestration and Its Response to Ocean Warming
Authors: Zhao Hanshuang , Zhang Zenghu , Nair Shailesh , Li Hongmei , He Chen , Shi Quan , Zheng Qiang , Cai Ruanhong , Luo Genming , Xie Shucheng , Jiao Nianzhi , Zhang Yongyu
Published: November 2024

Long‐term carbon sequestration by the ocean's recalcitrant dissolved organic carbon (RDOC) pool regulates global climate. Algae and bacteria interactively underpin RDOC formation. However, on the long‐term scales, the influence of their persistent interactions close to in situ state on ocean RDOC dynamics and accumulation remains unclear, limiting our understanding of the oceanic RDOC pool formation and future trends under global change. We show that a Synechococcus‐bacteria interaction model system viable over 720 days gradually accumulated high DOC concentrations up to 84 mg L−1. Concurrently, the DOC inertness increased with the RDOC ratio reaching > 50%. The identified Synechococcus‐bacteria‐driven RDOC molecules shared similarity with over half of those from pelagic ocean DOC. Importantly, we provide direct genetic and metabolite evidence that alongside the continuous transformation of algal carbon by bacteria to generate RDOC, Synechococcus itself also directly synthesized and released RDOC molecules, representing a neglected RDOC source with ~0.2–1 Gt y−1 in the ocean. However, we found that although ocean warming (+4°C) can promote algal and bacterial growth and DOC release, it destabilizes and reduces RDOC reservoirs, jeopardizing the ocean's carbon sequestration capacity. This study unveils the previously underestimated yet significant role of algae and long‐term algae‐bacteria interactions in ocean carbon sequestration and its vulnerability to ocean warming.
Rethinking Global Hotspots for Threatened Terrestrial Vertebrates
Authors: Huais Pablo Yair , Osorio‐Olvera Luis , Cordier Javier Maximiliano , Tomba Ana N. , Soberón Jorge , Loyola Rafael , Nori Javier
Published: November 2024

Aim

We aimed to delimit hotspots for terrestrial threatened vertebrate species (HTV) through novel macroecological and statistical approaches.

Location

Global.

Time Period

Present day (1979–2024).

Major Taxa Studied

Terrestrial threatened vertebrate species (n = 7188).

Methods

In comparison with previous delimitations of hotspots, we: (i) considered richness and degree of endemism together through a robust statistical framework; (ii) focused on a priority set of species extremely important in terms of conservation, based on IUCN threat status; and (iii) used a fine spatial scale which allowed us to define key sub‐areas within classic hotspots. We also assessed the degree of protection and human impact within the proposed HTV.

Results

We propose 20 global hotspots for threatened terrestrial vertebrates. In comparison with classic hotspots, proposed HTV have a significantly more limited distribution, covering ~27% of classic hotspots' area. In addition, a large proportion of HTV (~27%) does not match with classic hotspots. The overlap between HTV and protected areas (PAs) is low (< 11%), and extremely low when only strict protected areas are considered (< 1.5%). Also, a great degree of HTV exhibits high to extreme levels of human modification. On average, the velocity of climate change within HTV has been low, but attention must be given to notable areas presenting medium to high velocities. Interestingly, the geographical locations of highly endemic and rich areas considerably varied across individual vertebrate taxa. Yet, a high proportion of these priority areas for individual taxa are covered by the proposed HTV (74%–89%).

Main Conclusions

Our findings present key areas of the world for threatened terrestrial vertebrate species, many of these at high risk due to an interplay among low levels of protection, extreme levels of human modification and climate change. The proposed HTV are highly relevant in terms of decision‐making, serving as a guide for allocating the limited conservation resources.
Relative frequency, characteristics, and disease burden of patients with migraine unsuitable for triptan treatment: A systematic literature review
Authors: Lipton Richard B. , Gendolla Astrid , Abraham Lucy , Jenkins Aaron , Telfort Jersen , Blakeman Karin Hygge , Saccone Phillip A. , Pustulka Iwona , Fotheringham Iain , Engh Anita
Published: November 2024

Objective

This review was conducted to systematically identify evidence characterizing patients with migraine who are unsuitable for triptans.

Background

Triptans are not suitable as first‐line treatment for all patients with migraine due to contraindications, lack of efficacy, and/or poor tolerability. However, there is debate about the frequency and characteristics of these patients and the burden they experience.

Methods

MEDLINE, Embase, and conference abstracts (2011–2022) were reviewed for evidence on patients with migraine unsuitable for triptans for any reason. Data from publications describing the frequency and characteristics of this group, as well as the clinical, humanistic, or economic burden of disease in this population, were extracted.

Results

Of 1460 records screened, 29 publications met inclusion criteria. Persistence with triptans was low; 51%–66% of patients starting a new triptan did not refill it, and 43%–100% discontinued their initial triptan over 2 years. In one study, 14% of patients with migraine reported prior discontinuation/failure of ≥ 2 triptans due to inadequate efficacy or poor tolerability. Up to 15% of patients with migraine had triptan contraindications, and ≥ 20% of patients receiving triptans had contraindications. In four studies, 10%–44% of patients who tried triptans had insufficient response, although definitions varied. Patients who achieved a sufficient response typically did so with their first triptan; few became responders with additional triptans. Of patients who did not respond to one to two triptans and received another, 45% were dissatisfied with the final triptan. Approximately half of patients who tried two to three triptans had an insufficient response. Greater disability, impact of disease, and depression were reported in triptan discontinuers compared to those with sustained use. Worse quality of life scores and utility values were reported in triptan insufficient versus sufficient responders, as were greater migraine‐related costs, work impairment, and health‐care resource utilization.

Conclusion

The total population of patients unsuitable for triptans is uncertain, but the literature highlights a large group who cannot or do not persist with triptans, and current evidence suggests a high burden in this population and an unmet need for new therapeutic options. Further research is needed to determine the frequency of unsuitability for triptans more precisely and to assess the associated burden.
Deep brain stimulation for chronic refractory cluster headache: A case series about long‐term outcomes and connectivity analysis
Authors: Aibar‐Durán Juan Ángel , González Nerea , Mirapeix Rosa M. , Sánchez‐Mateos Noemi Morollón , Arsequell Clara Roig , Pichot Maria Borrell , Belvís Nieto Robert , Fenoy Gemma Piella , de Quintana Schmidt Cristian , Hernandez Fernando Muñoz , Fernández Fernando Seijoo , Rodríguez Rodríguez Rodrigo
Published: November 2024

Objective

The aim of this study was to provide long‐term clinical results—including “sweet spot” identification and connectomic imaging analysis—in a series of patients treated with deep brain stimulation for refractory chronic cluster headache.

Background

Deep brain stimulation is a relatively recent indication for the treatment of refractory chronic cluster headache. This indication has generated substantial debate in recent years due to uncertainty surrounding the mechanism of action and the lack of long‐term efficacy data.

Methods

Case retrospective series of adult patients diagnosed with refractory chronic cluster headache and treated with deep brain stimulation. Demographic and clinical data were registered preoperatively and at 3, 6, 12, and 24 months. The primary endpoint was reduction in headache load, a composite score of frequency, severity, and duration of each attack. Imaging analyses (sweet spot and connectomic analyses) were performed to identify the brain regions most closely correlated with the reduction in headache load and to identify the structural networks involved. Treatment response was categorized according to the reduction in headache load, as follows: poor (<30% reduction), partial (30–50%), or high (>50%).

Results

A total of 14 patients were included, with a mean (standard deviation [SD]) age of 42.4 (10.7) years and mean (SD) headache duration of 8.0 (5.8) years. Headache load scores decreased significantly from baseline to Month 24: mean (SD) 424.2 (325.9) versus 135.9 (155.7) (p = 0.001). In most patients (eight patients [58.0%]), headache load scores decreased by 50% after treatment. The other six patients showed either a partial (three [21.0%]) or poor (three [21.0%]) response. The optimized sweet spot was the lateral ventral tegmental area ((Montreal Neurological Institute) MNI coordinates of the center of mass: x = ± 9.0 mm, y = −10.6 mm, z = −3.5 mm). The connectomic analysis pointed to the probable implication of corticorubral tracts.

Conclusion

These findings suggest that a substantial proportion of patients with refractory chronic cluster headache obtain significant long‐term clinical benefits from deep brain stimulation. Good responders were characterized by a robust improvement in headache load within 3–6 months after surgery. The lateral ventral tegmental area was identified as the best target for this indication, with the likely participation of corticorubral tracts.
Digital Guides for Precise U‐Shaped Splitting and Simultaneous Implant Placement With Minimal Surgical Trauma
Authors: Feng Xin , Wan Ziqianhong , Wang Xiaoxia , Wang Jin , Gan Xueqi , Zhu Zhuoli
Published: November 2024

Objective

The aim of this report is to present the workflow of a surgical procedure involving U‐shaped splitting in an envelope flap with simultaneous implant placement using two digital guides for patients with insufficient bone width and labial concavity.

Clinical Consideration

Two digital guides and an envelope flap are proposed in this report. An implant drilling guide and an osteotomy guide guarantee the precise execution of surgical procedures. Using an envelope flap enhances the integrity of the labial mucoperiosteum, minimizing surgical trauma and improving the effect of bone augmentation.

Conclusion

With the assistance of two digital guides, precise U‐shaped splitting in an envelope flap can minimize surgical trauma and have a significant effect on horizontal bone augmentation.

Clinical Significance

This workflow considers the implant positions, the scope of osteotomy, and the kind of flap. It ensures minimal surgical trauma and excellent bone augmentation effect, which means predictable esthetic outcomes and stability in oral implantology, and provides a considerable solution for patients with insufficient bone width and labial concavity.
Content accuracy and readability of dietary advice available on webpages: A systematic review of the evidence
Authors: Fappa Evaggelia , Micheli Mary
Published: November 2024

Background

Concerns have been raised regarding the quality of health information published on the World Wide Web, while studies accumulating similar evidence for nutrition‐related information are scarce. The present review aimed to systematically accumulate and discuss the findings of studies evaluating the content quality of websites publishing nutrition‐related information, based on the PRISMA statement.

Methods

Studies that have assessed the accuracy and readability of dietary advice published on websites/webpages were evaluated. The SPIDER framework was used for the systematic search of studies, and those that evaluated websites/webpages that did not contain nutritional information, were videos or social media, referred to health professionals, or contained information on a specific theme (e.g., dietary supplements), were excluded.

Results

Twenty‐nine studies were included in this review, assessing information, published mainly in English, on 18 different diet‐related topics. Twenty of them classified websites and reported, also, results per category. Inconsistent information has been found on 16%–49.6% of websites, with this percentage rising to 54%–94% in the case of ‘weight loss’ information. Purely congruent with guidelines information was found on 18%–39.7% of websites. Commercial sites were inferior in terms of quality to the rest. The readability level was estimated as higher than the recommended in 9 out of 11 studies that assessed it.

Conclusions

Results of the present systematic review indicate that inaccurate and hard‐to‐read dietary advice is found on many websites, regardless of the dietary topic.
Applying natural language processing to understand symptoms among older adult home healthcare patients with urinary incontinence
Authors: Scharp Danielle , Song Jiyoun , Hobensack Mollie , Palmer Mary Happel , Barcelona Veronica , Topaz Maxim
Published: November 2024

Introduction

Little is known about the range and frequency of symptoms among older adult home healthcare patients with urinary incontinence, as this information is predominantly contained in clinical notes. Natural language processing can uncover symptom information among older adults with urinary incontinence to promote holistic, equitable care.

Design

We conducted a secondary analysis of cross‐sectional data collected between January 1, 2015, and December 31, 2017, from the largest HHC agency in the Northeastern United States. We aimed to develop and test a natural language processing algorithm to extract symptom information from clinical notes for older adults with urinary incontinence and analyze differences in symptom documentation by race or ethnicity.

Methods

Symptoms were identified through expert clinician‐driven Delphi survey rounds. We developed a natural language processing algorithm for symptom identification in clinical notes, examined symptom documentation frequencies, and analyzed differences in symptom documentation by race or ethnicity using chi‐squared tests and logistic regression models.

Results

In total, 39,179 home healthcare episodes containing 1,098,419 clinical notes for 29,981 distinct patients were included. Nearly 40% of the sample represented racially or ethnically minoritized groups (i.e., 18% Black, 14% Hispanic, 7% Asian/Pacific Islander, 0.3% multi‐racial, and 0.2% Native American). Based on expert clinician‐driven Delphi survey rounds, the following symptoms were identified: anxiety, dizziness, constipation, syncope, tachycardia, urinary frequency/urgency, urinary hesitancy/retention, and vision impairment/blurred vision. The natural language processing algorithm achieved excellent performance (average precision of 0.92). Approximately 29% of home healthcare episodes had symptom information documented. Compared to home healthcare episodes for White patients, home healthcare episodes for Asian/Pacific Islander (odds ratio = 0.74, 95% confidence interval [0.67–0.80], p < 0.001), Black (odds ratio = 0.69, 95% confidence interval [0.64–0.73], p < 0.001), and Hispanic (odds ratio = 0.91, 95% confidence interval [0.85–0.97], p < 0.01) patients were less likely to have any symptoms documented in clinical notes.

Conclusion

We found multidimensional symptoms and differences in symptom documentation among a diverse cohort of older adults with urinary incontinence, underscoring the need for comprehensive assessments by clinicians. Future research should apply natural language processing to other data sources and investigate symptom clusters to inform holistic care strategies for diverse populations.

Clinical Relevance

Knowledge of symptoms of older adult home healthcare patients with urinary incontinence can facilitate comprehensive assessments, health equity, and improved outcomes.
Technological innovations of hidden champions: Evidence from patent data
Authors: Lampe Hannes W. , Block Jörn , Willeke Tom , Clauss Thomas , Steinmetz Holger
Published: November 2024

The hidden champion concept has received much interest in practice. As market leaders in niche markets, hidden champions represent the success of the (German) Mittelstand. Innovation is a key element of their strategy and their focus and niche market strategy are associated with specific technological capabilities. However, thus far, little quantitative empirical evidence exists about the innovation output of hidden champions. Drawing on a capability perspective and using patent data, the present study analyzes differences between hidden champions and comparable non‐hidden champion firms in their technological innovation. Our results show that hidden champions have a significantly larger technological innovation output but do not have a higher efficiency in their innovation creation compared to other firms from the same industry, size, and age. Moreover, the innovations produced by hidden champions show higher levels of technological depth and indicate lower levels of technological breadth. The sources of technological knowledge of hidden champions seem to be more inward oriented. Finally, innovations of hidden champions have similar technological impact, novelty and quality compared to those of other firms. Overall, our study supports many of the anecdotal beliefs about the innovation of hidden champions contributing to a better understanding of what makes hidden champions different from other Mittelstand firms. Practical implications for hidden champions and Mittelstand firms are discussed.
Performance of questionnaires to predict sleep‐disordered breathing in acute stroke patients
Authors: Dekkers Martijn Petrus Josephus , Horvath Christian Michael , Woerz Vanessa S. , Bernasconi Corrado , Duss Simone B. , Schmidt Markus H. , Manconi Mauro , Brill Anne‐Kathrin , Bassetti Claudio L. A.
Published: November 2024

Sleep‐disordered breathing is common in stroke and may negatively affect its outcome. Screening for sleep‐disordered breathing in this setting is of interest but poorly studied. We aimed to evaluate the performance of eight obstructive sleep apnea screening questionnaires to predict sleep‐disordered breathing in acute stroke or transient ischaemic attack patients, and to assess the impact of stroke/transient ischaemic attack‐specific factors on sleep‐disordered breathing prediction. We analysed acute stroke/transient ischaemic attack patients (N = 195) from a prospective cohort (“Sleep Deficiency and Stroke Outcome study”). Assessments included anthropometrics, stroke‐specific parameters, sleep history, an in‐hospital respiratory polygraphy within the first week after stroke, and obstructive sleep apnea screening questionnaires (Berlin Questionnaire, Epworth Sleepiness Scale, STOP‐BANG, NoSAS, Sleep Apnea Clinical Score, No‐Apnea, Sleep Obstructive apnea score optimized for Stroke, SLEEP‐IN). In a binary classification task for respiratory event index ≥ 15 per hr, we evaluated the performance of the above‐mentioned questionnaires. We used logistic regression to identify predictors for sleep‐disordered breathing in this cohort. The areas under the curve for respiratory event index ≥ 15 per hr were: Berlin Questionnaire 0.60; STOP‐BANG 0.72; NoSAS 0.69; No‐Apnea 0.69; Sleep Apnea Clinical Score 0.75; Epworth Sleepiness Scale 0.50; Sleep Obstructive apnea score optimized for Stroke 0.58; and SLEEP‐IN 0.67. The No‐Apnea had the lowest false omission rate (0.13), a sensitivity of 0.97 and a specificity of 0.12. In multiple logistic regression analysis (respiratory event index ≥ 15 per hr), age, neck circumference, National Institutes of Health Stroke Scale at admission, prior stroke, cardioembolic stroke aetiology and observed apneas were associated with sleep‐disordered breathing. The logistic regression model performed similar (area under the curve 0.80) to Sleep Apnea Clinical Score (p = 0.402) and STOP‐BANG (p = 0.127), but outperformed the other questionnaires. Neither existing questionnaires nor our statistical model are sufficient to accurately diagnose sleep‐disordered breathing after stroke, thus requiring sleep study evaluation. The No‐Apnea questionnaire may help to identify patients amenable to sleep testing.
Dose‐exposure‐response of CARDALIS® (benazepril/spironolactone) on the classical and alternative arms of the renin‐angiotensin‐aldosterone system in healthy dogs
Authors: Manson Elizabeth , Ward Jessica L. , Merodio Maria , Guillot Emilie , Blondel Thomas , Allenspach Karin , Domenig Oliver , Mochel Jonathan P.
Published: November 2024

Background

Benazepril exhibits a dose‐dependent effect on biomarkers of the circulating renin‐angiotensin‐aldosterone system (RAAS) in dogs.

Hypothesis/Objectives

To characterize the dose‐exposure‐response relationship of a fixed‐dose combination product including benazepril and spironolactone (CARDALIS®) on RAAS biomarkers in dogs.

Animals

Eighteen purpose‐bred healthy beagle dogs.

Methods

Three groups of 6 dogs received different doses of CARDALIS® for 14 days following induction of RAAS activation by feeding a low‐sodium diet: (a) benazepril 0.25 mg/kg + spironolactone 2 mg/kg PO q24h (label dose); (b) benazepril 0.25 mg/kg + spironolactone 2 mg/kg PO q12h; or (c) benazepril 0.5 mg/kg + spironolactone 4 mg/kg PO q12h. Blood samples were collected at baseline and serial time intervals after CARDALIS® dosing to measure serum RAAS biomarkers and plasma concentrations of active drug metabolites. Time‐weighted averages for serum RAAS biomarkers after CARDALIS® dosing at steady state were compared between dosage groups using Wilcoxon rank‐sum testing.

Results

Compared to the label dose, the highest dose of CARDALIS® was associated with a 30% decrease in angiotensin II (P = .03), 94% increase in angiotensin 1‐7 (P = .03), 71% decrease in surrogate activity of ACE (P = .002), and 116% increase in circulating aldosterone (P = .02). CARDALIS® was well‐tolerated at all doses with no clinically relevant changes in renal values or serum electrolytes.

Conclusions and Clinical Importance

The combined CARDALIS® product leads to dose‐dependent alterations of RAAS metabolites. These results could help inform clinical trials in dogs with heart disease.
Efficacy of Procaine, With and Without Epinephrine, Compared to Lidocaine in Local Anesthesia for Calves Before Thermocautery Disbudding
Authors: Adam Magdy , Jokela Annemari , Salla Kati , Aho Riikka , Raekallio Marja , Hänninen Laura , Hokkanen Ann‐Helena
Published: November 2024

Within the European Union, the use of lidocaine in food‐producing animals is restricted due to concerns over human safety. This study compared the clinical effectiveness of procaine, with and without epinephrine, against lidocaine in pain alleviation during thermocautery disbudding in xylazine‐sedated calves. The efficacy of local blocks was assessed through needle pricks, and the behavioral reactions to disbudding were scored. Post‐disbudding pain was subjectively evaluated, and pressure pain threshold and tactile sensitivity around the horn bud were assessed at intervals. Blood was collected at intervals for plasma cortisol analysis. No significant differences were found between the groups in the needle prick test (p = 0.329) and the disbudding score (p = 0.855). Pain scores and quantitative sensory tests showed no significant differences between the lidocaine and procaine‐epinephrine groups. Conversely, tactile sensitivity and pain scores were significantly higher, and pressure pain thresholds were significantly lower with procaine alone than in other groups. Elevated cortisol concentrations were observed in all groups before disbudding compared to the baselines. The results suggest that procaine combined with epinephrine appears to be a safe and effective alternative to lidocaine for calf disbudding. Cortisol concentrations as an indicator of pain in xylazine‐sedated calves appear inadequate.
A participatory democracy with an intersectional approach
Authors: Castañeda Hernández Mireya
Published: November 2024

The article inserts the concept of intersectionality contributed by Afro‐descendant feminism to study whether affirmative action is open to other vulnerable groups besides gender in Mexico. An explanatory investigation of the concept of intersectionality correlated with multiple affirmative action is carried out, and a case study considers the decisions made by two electoral institutions in Mexico. Crenshaw's theories are confirmed, including a case study carried out in Mexico focused on decisions by electoral authorities that have promoted the establishment of multiple affirmative actions in electoral matters. A ruling by the Electoral Tribunal in which the discussion focused on the implementation of the intersectionality concept due to the application of multiple affirmative actions is also highlighted. Affirmative action must be understood in a broad vision open to different vulnerable groups, and the concept of intersectionality must be considered when there is more than one reason for vulnerability so that better protection can be provided.
Enhanced Biomechanical Stability in Proximal Humeral Fractures: Finite Element Analysis of a Novel Endosteal Anatomical Support Nail for Improved Fixation in Elderly Patients
Authors: Chen Jiawen , Wang Zhonghe , Li Changda , He Peiyu , Chen Zhongxuan , Sun Lijun , Cao Xiaoyan , Tian Na , Dong Xiang , Tang Peifu , Chen Hua
Published: November 2024

Objectives

Intramedullary nailing is preferred for treating elderly proximal humeral fractures, but secondary reductions are common, particularly in elderly and osteoporotic patients. This occurs due to the intramedullary nail fixation's insufficient anti‐varus and anti‐rotational capacities and high stress at the bone–implant interface. We aim to enhance the anti‐varus and anti‐rotational stability of the fixation structure while reducing the stresses on the bone and internal fixation through structural design.

Materials and Methods

We developed a novel endosteal anatomical support nail (EASN) that integrates an endosteal torus construct into the proximal portion of the angle‐stable proximal humerus nail. The endosteal torus construct includes endosteal anatomical support (EAS) with a flat plane that allows direct fixation of the humeral head fragments and is shaped to conform to the medial side of the medullary cavity of the proximal humerus. We conducted finite element analysis to assess the biomechanical stability of four constructs: EAS with a calcar screw (CS), EAS without CS, non‐EAS with CS, and non‐EAS without CS. This analysis determined the contribution of the EAS to the mechanical stability of the proximal humerus in two‐part PHF with medial column disruption. Specimens were subjected to loads simulating partial‐weight‐bearing (as in rising from a chair or using crutches) and full‐weight‐bearing (as in rising from bed). We evaluated the stiffness of the construct, displacement at the fracture site, von Mises stress, and stress distribution.

Results

Under compressive or rotational loads, the EAS construct, with or without CS, was significantly stiffer than the non‐EAS construct. Displacement at the fracture site was significantly less with the EAS fixation than with the non‐EAS fixation. However, the stiffness and displacement at the fracture site of the EAS fixation without CS were comparable to those of the non‐EAS construct with CS. The EAS construct reduced the load on the nail and decreased the risk of implant failure. Both von Mises stress and stress distribution were significantly lower following fixation with the EAS constructs.

Conclusions

This study introduces a novel EAS concept to enhance the anti‐varus and anti‐rotational capabilities of the humeral head and distribute stress at the bone–implant interface in treating elderly PHFs. This strategy shows promise based on our limited analysis.
BcVQ11A‐BcWRKY23‐BcWRKY25 Module Is Involved in Thermotolerance by Regulating Phenylalanine Ammonia‐Lyase Activity in Non‐Heading Chinese Cabbage
Authors: Gao Zhanyuan , Wang Haiyan , Chen Xiaoshan , Ding Qiang , Li Entong , Shen Yunlou , Jiang Cheng , Li Ying , Zhang Changwei , Hou Xilin
Published: November 2024

High temperature can significantly affect the quality and yield of plants. However, there has been limited research investigating the thermotolerance of non‐heading Chinese cabbage (NHCC). This study, identified BcWRKY23 through transcriptome analysis in NHCC with varying levels of thermotolerance. Overexpression and silencing experiments demonstrated that BcWRKY23 positively regulates the thermotolerance of NHCC by activating its own expression under short‐term heat stress (HS). Additionally, BcWRKY23 was found to bind to the promoter of BcWRKY25 and activate its expression, which also enhanced thermotolerance. BcWRKY23 and BcWRKY25 enhanced the expression of HSR genes to improve thermotolerance. Furthermore, BcPAL1 was shown to be activated by BcWRKY23, while BcPAL2 was activated by both BcWRKY23 and BcWRKY25. Overexpression of BcPAL1 and BcPAL2 in NHCC significantly increased thermotolerance, accompanied by an enhancement of phenylalanine ammonia‐lyase (PAL) activity. Moreover, under long‐term HS, the significant accumulation of BcVQ11A was observed, and the interaction between BcVQ11A and BcWRKY23 as well as BcWRKY25 inhibited the activation of them to target genes, resulting in decreased PAL activity. This study proposes a HS response pathway involving BcVQ11A‐BcWRKY23‐BcWRKY25‐BcPAL1/BcPAL2, providing valuable insights into the molecular mechanisms underlying thermotolerance in plants.
Association between peripheral activated naive and double negative 2 B‐cell subsets and clinical parameters in lupus nephritis patients
Authors: Wangriatisak Kittikorn , de Vries Charlotte , Sharma Ravi Kumar , Huang Wenqi , Grönwall Caroline , Pisitkun Prapaporn , Gunnarsson Iva , Malmström Vivianne , Chootong Patchanee , Faustini Francesca
Published: November 2024

Altered composition of B‐cell compartments is a known feature in patients with systemic lupus erythematosus (SLE). However, deep characterisation of B‐cell subsets and their relation to clinical manifestations and disease activity in patients is limited. In this study, we analysed peripheral B‐cell subsets phenotype in SLE (n = 35) and healthy controls (HCs, n = 15) by spectral flow cytometry. Disease activity was stratified as inactive (SLEDAI‐2 K score 0, n = 2), mild (SLEDAI‐2 K score 1–5, n = 12), moderate (SLEDAI‐2 K score 6–10, n = 6) or high (SLEDAI‐2 K > 10, n = 15). An elevated proportion of activated naive (aNAV), double negative 2 (DN2) and plasmablasts (PB) was observed in patients with high disease activity, compared to other groups of patients and HCs. An upregulation of BTLA was found on both aNAV and DN2 and shifted to lower levels with increasing disease activity. In lupus nephritis (LN) patients (n = 21), aNAV B‐cells were especially expanded and positively correlated with DN2 (r = 0.5, p = 0.019) and PB (r = 0.43, p = 0.048). Also, correlation was observed between DN2 and PB (r = 0.6, p = 0.003). Moreover, aNAV frequencies positively correlated with SLEDAI‐2 K score, and negatively with the complement fractions C3 and C4. Further, aNAV, DN2 and PB were more expanded in association with positive anti‐dsDNA antibodies, rather than other antibody specificities (anti‐Sm). These data suggest roles of extrafollicular B cells as key players in disease development of LN. Their association with presence of anti‐dsDNA antibodies may indicate their value as candidate biomarkers of kidney involvement in SLE.
Profiles of father involvement among unmarried Black fathers and child social–emotional functioning
Authors: Yoon Susan , Wang Jingyi , Chang Yujeong , Lee Joyce Y. , Nho Choong Rai , Chung Ick‐Joong , Schoppe‐Sullivan Sarah J.
Published: November 2024

This study examined patterns of father involvement among 2040 unmarried non‐Hispanic Black fathers (M = 25.27 years; SD = 6.51 years) with low income, and their associations with young children's (age 3 years; 50.34% girls) social–emotional functioning. Latent profile analysis revealed four father involvement profiles: high involvement (50.60%); nonresident, moderate involvement (18.09%); highly engaged, but low cognitive stimulation (25.49%); and nonresident, very low involvement (3.82%). Children of highly involved Black fathers exhibited optimal social–emotional functioning compared to children of fathers in the other profiles. Children of fathers in the highly engaged, but low cognitive stimulation profile showed poorer social–emotional functioning. Our findings showed that Black fathering is a diverse experience with much heterogeneity, suggesting the need for fatherhood programs responsive to different fathering profiles.
Discovering journals: A strategy for enhancing the introductory statistics course for undergraduate students
Authors: Setiawan Ezra Putranda
Published: November 2024

Undergraduate students outside Statistics major frequently take only one class of Basic Statistics or Introductory Statistics during their studies. As a consequence, many of them have little knowledge about advanced statistical methods, such as logistic regression, nonparametric procedures, and multivariate analysis, although they might need to perform it in the future. We have developed a teaching strategy to introduce these topics to first‐year students who take the Introductory Statistics course by asking them to discovering scientific journals in groups and present them. A discussion feature in the Moodle e‐learning systems really helps us to carry out this strategy effectively. We discuss some benefits of this strategy as well as some pitfalls that can be occurred during its implementation.
A Golgi vesicle‐membrane‐localized cytochrome B561 regulates ascorbic acid regeneration and confers Verticillium wilt resistance in cotton
Authors: Liu Hanqiao , Zhang Wenshu , Zeng Jianguo , Zheng Qihang , Guo Zhan , Ruan Chaofeng , Li Weixi , Wang Guilin , Wang Xinyu , Guo Wangzhen
Published: November 2024

Ascorbic acid (AsA) serves as a key antioxidant involved in the various physiological processes and against diverse stresses in plants. Due to the insufficiency of AsA de novo biosynthesis, the AsA regeneration is essential to supplement low AsA synthesis rates. Redox reactions play a crucial role in response to biotic stress in plants; however, how AsA regeneration participates in hydrogen peroxide (H2O2) homeostasis and plant defense remains largely unknown. Here, we identified a Golgi vesicle‐membrane‐localized cytochrome B561 (CytB561) encoding gene, GhB561‐11, involved in AsA regeneration and plant resistance to Verticillium dahliae in cotton. GhB561‐11 was significantly downregulated upon V. dahliae attack. Knocking down GhB561‐11 greatly enhanced cotton resistance to V. dahliae. We found that suppressing GhB561‐11 inhibited the AsA regeneration, elevated the basal level of H2O2, and enhanced the plant defense against V. dahliae. Further investigation revealed that GhB561‐11 interacted with the lipid droplet‐associated protein GhLDAP3 to collectively regulate the AsA regeneration. Simultaneously silencing GhB561‐11 and GhLDAP3 significantly elevated the H2O2 contents and dramatically improved the Verticillium wilt resistance in cotton. The study broadens our insights into the functional roles of CytB561 in regulating AsA regeneration and H2O2 homeostasis. It also provides a strategy by downregulating GhB561‐11 to enhance Verticillium wilt resistance in cotton breeding programs.