bluuebunny/crossref_metadata_2025 huggingface dataset:
Classic Light Transmission Platelet Aggregometry: Do We Still Need it?
Authors: Gebetsberger Jennifer , Prüller Florian
Published: December 2023

For more than 50 years, light transmission aggregometry has been accepted as the gold standard test for diagnosing inherited platelet disorders in platelet-rich plasma, although there are other functional approaches performed in whole blood. In this article, several advantages and disadvantages of this technique over other laboratory approaches are discussed in the view of recent guidelines, and the necessity of functional assays, such as light transmission aggregometry in the era of molecular genetic testing, is highlighted.
Das Mammakarzinom und die genetische BRCA1/2-Testung in der klinischen Routine: warum, wann und für wen?
Authors: Lux Michael P. , Fasching Peter A.
Published: December 2023

Pathogene Varianten der Tumorsuppressorgene BRCA1 und BRCA2 sind für den Großteil der hereditären Mammakarzinome verantwortlich und gewinnen zunehmend an Bedeutung für die Bestimmung der Eignung einer zielgerichteten Therapie mit Inhibitoren der Poly-ADP-Ribose-Polymerasen (PARPi). Patient*innen mit einem HER2-negativen Mammakarzinom und BRCA1/2-Keimbahnmutation können deutlich von einer PARPi-Therapie profitieren, und die Ergebnisse der Zulassungsstudien OlympiAD und EMBRACA aus der fortgeschrittenen Therapiesituation wurden kürzlich mit den aktuellen OlympiA-Daten für die Therapie von Patient*innen mit frühen Krankheitsstadien und hohem Rezidivrisiko erweitert.

Somit ist die BRCA1/2-Keimbahntestung zur Therapieplanung nun auch für Patient*innen mit Mammakarzinom im Frühstadium und damit direkt für das Überleben der Erkrankten relevant. Daten aus der Versorgungsforschung zeigen jedoch, dass die BRCA1/2-Testraten stark geprägt sind von Familienanamnese, Subtyp (insbesondere triple-negativ) und Erkrankungsalter (insbesondere jüngere Erkrankte) – trotz vorliegender klarer Empfehlungen für eine BRCA1/2-Keimbahntestung zur Indikationsstellung einer PARPi-Therapie.

Dieser Artikel beschreibt die klinischen Implikationen der Identifizierung einer BRCA1/2-Keimbahnmuation für Patient*innen mit einem Mammakarzinom, die aktuellen Empfehlungen zur molekularen Diagnostik sowie deren praktische Umsetzung. Die Behandlung der an einem Mammakarzinom Erkrankten hat in den letzten Jahren große Fortschritte erzielt und bietet nun individuelle Therapiekonzepte, welche nur durch die gezielte Identifikation von Einzelparametern zur Anwendung kommen können.

Da der Nachweis einer BRCA1/2-Keimbahnmutation für die individuelle Therapieplanung von entscheidender Bedeutung ist, ist diese bei entsprechender Indikation so früh wie möglich zu veranlassen. Nur so können für eine PARPi-Therapie geeignete Patient*innen identifiziert und eine bestmögliche Therapie garantiert werden. Dies gilt auch für Patient*innen mit negativer Familienanamnese, HR-positiver Erkrankung und höherem Erkrankungsalter.
FAF1 Gene Involvement in Pituitary Corticotroph
Tumors
Authors: Nguyen Matthew , Maria Andrea Gutierrez , Faucz Fabio R. , Trivellin Giampaolo , Stratakis Constantine A. , Tatsi Christina
Published: December 2023

Cushing’s disease (CD) is caused by rare pituitary corticotroph tumors
that lead to corticotropin (ACTH) excess. Variants in FAF1, a
pro-apoptotic protein involved in FAS-induced cell death, have been implicated
in malignant disorders but the involvement of FAF1 in pituitary tumors
has not been studied. Genetic data from patients with CD were reviewed for
variants in FAF1 gene. Knockout mice (KO) were followed to assess the
development of any pituitary disorder or cortisol excess. AtT-20 cells were used
to study the effects of the variants of interest on ACTH secretion and cell
proliferation. Three variants of interest were identified in 5 unique patients,
two of which had rare allele frequency in genomic databases and were predicted
to be likely pathogenic. KO mice were followed over time and no difference in
their length/weight was noted. Additionally, KO mice did not develop any
pituitary lesions and retained similar corticosterone secretion with wild type.
AtT-20 cells transfected with FAF1 variants of interest or WT expression
plasmids showed no significant difference in cell death or Pomc gene expression.
However, in silico prediction models suggested significant differences in
secondary structures of the produced proteins. In conclusion, we identified two
FAF1 variants in patients diagnosed with CD with a potential
pathogenic effect on the protein function and structure. Our in vitro and in
vivo studies did not reveal an association of FAF1 defects with pituitary
tumorigenesis and further studies may be needed to understand any
association.
Berufliche Teilhabe nach einer medizinischen Rehabilitation aufgrund
von onkologischen Erkrankungen: Repräsentative Analysen auf Basis der
Routinedaten der Deutschen Rentenversicherung
Authors: Fauser David , Zollmann Pia , Streibelt Marco , Bethge Matthias
Published: December 2023

Ziel der Studie Onkologische Erkrankungen gehen mit vielfältigen
körperlichen, psychosozialen und beruflichen Belastungen einher, die die
berufliche Teilhabe gefährden und mit rehabilitativen Interventionen
gezielt adressiert werden müssen. Für Personen, die aufgrund
einer onkologischen Erkrankung eine Rehabilitation in Trägerschaft der
Deutschen Rentenversicherung (DRV) absolvierten, soll ermittelt werden, (a)
welche sozialmedizinischen Risiken im Vorfeld der Rehabilitation bestehen, (b)
wie gut die berufliche Teilhabe im Anschluss gelingt und (c) welche
Informationen mit der beruflichen Teilhabe assoziiert sind.

Methodik Die Fragen wurden anhand der Reha-Statistik-Datenbasis der DRV
beantwortet. Eingeschlossen wurden Rehabilitand*innen, die in 2017 eine
medizinische Rehabilitation aufgrund einer onkologischen Erkrankung
abgeschlossen hatten. Die Analysen wurden für die Gesamtgruppe sowie
differenziert nach den Diagnosegruppen Bösartige Neubildungen (BN) der
Brustdrüse, der Prostata, des Darms und der Lunge durchgeführt.
Berufliche Teilhabe wurde sowohl über eine monatliche Zustandsvariable
bis 24 Monate nach der Rehabilitation als auch als Quote aller Personen, die
nach 12 respektive 24 Monaten im Erhebungsmonat und den 3 vorhergehenden Monaten
sozialversicherungspflichtig beschäftigt waren, operationalisiert.
Für die Analyse der Einflussfaktoren auf stabile berufliche Teilhabe
wurden multiple logistische Regressionsmodelle mit schrittweisem Einschluss,
getrennt für die Quoten nach 12 und 24 Monaten für Frauen und
Männer, berechnet.

Ergebnisse Die Analyse berücksichtigt 63.587 Datensätze
(darunter BN der Brustdrüse: n=20.545, 32%; Prostata:
n=6.434, 10%; Darm: n=4.727, 7%; Lunge:
n=2.866, 5%). Die Anteile an Rehabilitand*innen mit
Fehlzeiten von sechs und mehr Monaten im Jahr vor der Rehabilitation waren
55% (Lunge), 49% (Darm), 46% (Brustdrüse) und
13% (Prostata). Zwei Jahre nach der Rehabilitation lagen die
Rückkehrquoten in Arbeit bei 66% (Brustdrüse),
54% (Prostata), 50% (Darm) und 24% (Lunge). Die
stärksten Einflussfaktoren auf stabile berufliche Teilhabe waren die
Fehlzeiten und das Entgelt vor Rehabilitation sowie das Alter.

Schlussfolgerungen Zwei Jahre nach an einer onkologischen Rehabilitation
befinden sich 5 bis 6 von 10 Betroffenen in stabiler beruflicher Teilhabe.
Relevante Einflussfaktoren auf die Entwicklung sind die
Arbeitsunfähigkeit und Entgelthöhe im Vorfeld der onkologischen
Rehabilitation. Die Ergebnisse legen eine stärkere Ergänzung der
onkologischen Rehabilitation um arbeitsbezogene Aspekte und eine begleitende
Unterstützung von Rehabilitand*innen insbesondere im ersten Jahr
nach Abschluss der Rehabilitation nahe.
Hyperemesis gravidarum – eine interprofessionelle und
interdisziplinäre Herausforderung
Authors: Rath Werner , Maul Holger , Abele Harald , Pauluschke Jan
Published: December 2023

Die Hyperemesis gravidarum (HG) ist eine multifaktorielle Erkrankung,
charakterisiert durch persistierende Übelkeit/Erbrechen,
Dehydratation, Gewichtsverlust von mindestens 5%,
Elektrolytstörungen und Ketoazidose. Die Prävalenz liegt
weltweit zwischen 0,3 und 10%. Die Diagnose wird anhand der Anamnese,
der klinischen Symptome, der körperlichen Untersuchung und der typischen
Laborveränderungen gestellt. Grundpfeiler der Therapie sind
Ernährungsberatung, Beratung zum Lebensstil,
psychologische/psychosoziale Unterstützung der Schwangeren und
die Gabe von Antiemetika im Sinne eines sich an dem Schweregrad der Symptome
orientierenden Stufenkonzepts. Ein häufiger Wechsel von Antiemetika ist
zu vermeiden. Die Behandlung der HG erfordert eine enge interprofessionelle und
interdisziplinäre Zusammenarbeit.
Comparison of Microwave and Radiofrequency Ablation for the Treatment of Small- and Medium-Sized Hepatocellular Carcinomas in a Prospective Randomized Trial
Authors: Vogl Thomas J. , Martin Simon S. , Gruber-Rouh Tatjana , Booz Christian , Koch Vitali , Nour-Eldin Nour-Eldin A. , Hussainy Said M. N.
Published: December 2023

Purpose To compare the therapeutic response and clinical outcome of CT-guided percutaneous microwave (MWA) and radiofrequency ablation (RFA) for the treatment of small- and medium-sized HCC.

Materials and Methods In this prospective trial, 50 patients with HCC were randomly assigned to MWA or RFA treatment. MRI was performed 24 h before and after ablation and subsequently in 3-month intervals. Ablation volumes, ablation durations, adverse events (AE), technique efficacy, technical success, local tumor progression (LTP), disease-free survival (DFS), intrahepatic distant recurrence (IDR), and overall survival (OS) rates were evaluated.

Results The mean ablation volume was 66.5 cm³ for MWA and 29.2  cm³ for RFA (p < 0.01). The mean ablation durations for MWA and RFA were 11.2 ± 4.0 min and 16.3 ± 4.7 min, respectively (p < 0.01). Six mild AEs were documented (p > 0.05). All treatments had a technical success rate and a technique efficacy rate of 100 % (50/50, p = 1.00). LTP within 2 years occurred in 1/25 (4 %) in the MWA group and in 4/25 (16 %) in the RFA group (p = 0.06). IDR within 2 years was 8/25 (32 %) for MWA and 14/25 (56 %) for RFA (p < 0.05). The median DFS was 24.5 months and 13.4 months for MWA and RFA, respectively (p = 0.02). The 1-, 2-, 3-year OS rates were 100 %, 80 %, 72 % in the MWA group and 72 %, 64 %, 60 % in the RFA group, respectively (p ≥ 0.14).

Conclusion The clinical outcome after MWA or RFA for HCC treatment was very similar with no significant differences in LTP or OS. However, MWA shows a trend toward better DFS with fewer IDRs than RFA.

Key Points:
Applicability and robustness of an artificial intelligence-based assessment for Greulich and Pyle bone age in a German cohort
Authors: Pape Johanna , Hirsch Franz Wolfgang , Deffaa Oliver Johannes , DiFranco Matthew D. , Rosolowski Maciej , Gräfe Daniel
Published: December 2023

Purpose The determination of bone age (BA) based on the hand and wrist, using the 70-year-old Greulich and Pyle (G&P) atlas, remains a widely employed practice in various institutions today. However, a more recent approach utilizing artificial intelligence (AI) enables automated BA estimation based on the G&P atlas. Nevertheless, AI-based methods encounter limitations when dealing with images that deviate from the standard hand and wrist projections. Generally, the extent to which BA, as determined by the G&P atlas, corresponds to the chronological age (CA) of a contemporary German population remains a subject of continued discourse. This study aims to address two main objectives. Firstly, it seeks to investigate whether the G&P atlas, as applied by the AI software, is still relevant for healthy children in Germany today. Secondly, the study aims to assess the performance of the AI software in handling non-strict posterior-anterior (p. a.) projections of the hand and wrist.

Materials and Methods The AI software retrospectively estimated the BA in children who had undergone radiographs of a single hand using posterior-anterior and oblique planes. The primary purpose was to rule out any osseous injuries. The prediction error of BA in relation to CA was calculated for each plane and between the two planes.

Results A total of 1253 patients (aged 3 to 16 years, median age 10.8 years, 55.7 % male) were included in the study. The average error of BA in posterior-anterior projections compared to CA was 3.0 (± 13.7) months for boys and 1.7 (± 13.7) months for girls. Interestingly, the deviation from CA tended to be even slightly lower in oblique projections than in posterior-anterior projections. The mean error in the posterior-anterior projection plane was 2.5 (± 13.7) months, while in the oblique plane it was 1.8 (± 13.9) months (p = 0.01).

Conclusion The AI software for BA generally corresponds to the age of the contemporary German population under study, although there is a noticeable prediction error, particularly in younger children. Notably, the software demonstrates robust performance in oblique projections.

Key Points 

Citation Format
Working Memory, Attention Skills, and Language Proficiency in Children with Unilateral and Bilateral Cochlear Implants
Authors: Dikderi Cagla , Ozkan Atak Hilal B. , Yucel Esra
Published: December 2023

Background Previous studies observed that children with cochlear implants (CIs) have poor language, working memory, and attention skills. The ability to perform cognitive tasks, such as attention and memory, plays a crucial role in the academic achievement and everyday life of children with hearing impairment.

Purpose This study aimed to evaluate and compare the effects of age at the time of implantation and bilateral hearing on cognitive skills, such as language development, working memory, and selective attention, among children with CIs.

Research Design Language skills were assessed using the Test of Language Development-Primary: Fourth Edition (TOLD-P:4), working memory using the Visual-Aural Digit Span Test-Revised Form (VADS-R), and selective attention skills using the Stroop Test TBAG Form.

Study Sample A total of 58 participants, comprised of 21 children with early unilateral CIs (before 2 years), 18 children with late unilateral CIs (after 2 years), and 19 children with bilateral CIs, between the ages of 6 and 9 years, were included in the study.

Data Collection and Analysis According to the age at the time of implantation and whether or not the participant was unilaterally or bilaterally implanted, the mean scores, percentage values, and resultant scores of the participants were calculated using the Mann–Whitney U test. The number of repeated backward digit spans for the VADS-R test, completion times, number of errors and corrections for the Stroop test, raw scores, scaled scores corresponding to raw scores at the relevant age, descriptive terms for the TOLD-P:4 test, and within-group comparisons for all tests were examined.

Results There were significant differences in language, working memory, and attention skills between individuals with early and late unilateral cochlear implantation, whereas there were no significant differences in many subtests between individuals with early unilateral and bilateral cochlear implantation.

Conclusion These findings demonstrate the importance of early cochlear implantation and bilateral hearing on the development of cognitive processes, such as language development, selective attention, and memory skills, which are important factors that may contribute to children's academic performance and overall success.
Evaluation of a Patient Decision Aid for Refractive Eye Surgery
Authors: Subbaraman Bhavani , Ahmed Kamran , Heller Matthew , Essary Alison C. , Patel Vimla L. , Wang Dongwen
Published: December 2023

Background We developed a prototype patient decision aid, EyeChoose, to assist college-aged students in selecting a refractive surgery. EyeChoose can educate patients on refractive errors and surgeries, generate evidence-based recommendations based on a user's medical history and personal preferences, and refer patients to local refractive surgeons.

Objectives We conducted an evaluative study on EyeChoose to assess the alignment of surgical modality recommendations with a user's medical history and personal preferences, and to examine the tool's usefulness and usability.

Methods We designed a mixed methods study on EyeChoose through simulations of test cases to provide a quantitative measure of the customized recommendations, an online survey to evaluate the usefulness and usability, and a focus group interview to obtain an in-depth understanding of user experience and feedback.

Results We used stratified random sampling to generate 245 test cases. Simulated execution indicated EyeChoose's recommendations aligned with the reference standard in 243 (99%). A survey of 55 participants with 16 questions on usefulness, usability, and general impression showed that 14 questions recorded more than 80% positive responses. A follow-up focus group with 10 participants confirmed EyeChoose's useful features of patient education, decision assistance, surgeon referral, as well as good usability with multimedia resources, visual comparison among the surgical modalities, and the overall aesthetically pleasing design. Potential areas for improvement included offering nuances in soliciting user preferences, providing additional details on pricing, effectiveness, and reversibility of surgeries, expanding the function of surgeon referral, and fixing specific usability issues.

Conclusion The initial evaluation of EyeChoose suggests that it could provide effective patient education, generate appropriate recommendations, connect to local refractive surgeons, and demonstrate good system usability in a test environment. Future research is required to enhance the system functions, fully implement and evaluate the tool in naturalistic settings, and examine the findings' generalizability to other populations.
Cross-cultural Adaptation and Psychometric Evaluation of the Kurdish Version of the Disabilities of Arm, Shoulder, and Hand (DASH-KU) Scale
Authors: Hasan Rebwar A. , Barawi Omer A. , Hasan Jalal A.
Published: December 2023

Background The disabilities of arm, shoulder, and hand (DASH) questionnaire addresses the patient's disabilities and symptoms to evaluate the extent and the impact of injuries in the patient's daily-life activities. This study aims to develop a valid and reliable adaptation of DASH into the Kurdish language and culture (DASH-KU).

Methods American Association of Orthopedic Surgeons Outcomes Committee guideline was used for the cross-cultural adaptation of DASH to the Kurdish version. This study was conducted at the Shahid Saifaddin consultation clinic in Sulaymaniyah, Iraq between April and October 2022. A total of 300 participants, who were included in the study using an available sampling method, completed the self-report DASH-KU questionnaire during two consecutive assessments with a 24-hour interval.

Results The DASH-KU questionnaire demonstrated excellent internal consistency (Cronbach's α = 0.99) and test–retest reliability (intraclass correlation = 0.99). A strong correlation between DASH-KU scores and the patient-rated wrist/hand evaluation tool (r = 0.792) supported its construct validity. Bland–Altman plots showed good agreement between assessments with no floor (3%) or ceiling (0%) effects. Factor analysis found the scale had high adequacy (0.700) and significant sphericity (p < 0.001). The major factor explained 40% of variance with an eigenvalue of 13.14. Additionally, a five-item model explained 81.23% of DASH-KU variance, though responsiveness was suboptimal, possibly due to the short 24-hour interval between measurements.

Conclusion Our results demonstrate that DASH-KU has excellent reliability and validity in identifying upper limb injuries, and the psychometric properties of DASH-KU were similar to its original version.
Pictet–Spengler-Based Multicomponent Domino Reactions to Construct Polyheterocycles
Authors: Hu Jun-Duo , Huang Li-Liang , Feng Huang-Di
Published: December 2023

The Pictet–Spengler reaction is one of the important methodological arsenals in synthetic and medicinal chemistry, acting as an amenable tool for preparing tetrahydroisoquinoline, tetrahydro-β-carbolines, polycyclic skeletons, and value-added products. More than 100 years after its initial discovery, the Pictet–Spengler reaction's response has not withdrawn from the stage, but it has once again become the focus of attention with new features. The review summarizes recent advances in Pictet–Spengler-based multicomponent reactions from 2007 to 2022, including three-component and four-component Pictet–Spengler cyclization reactions in the presence of metal catalysts, organocatalysts, biological enzyme catalysts, and so on. These Pictet–Spengler-based multicomponent protocols provide an atom-/step economic approach for the synthesis of a library of new chemical entities.
Screening for Mutations in Hereditary Cancer Susceptibility Genes in a Region with High Endogamy in Brazil
Authors: Oliveira Polyanna , Correa Paula , Acosta Angelina , Freitas Juliana , Machado-Lopes Taísa , Bomfim-Palma Thais , Ribeiro-dos-Santos Ândrea , Santos Sidney , Nascimento Roberto , Nascimento Ivana , Abe-Sandes Kiyoko
Published: December 2023

Introduction Cancer is a multifactorial disease dependent on the influence of genetic and environmental factors. About 10% of cancers are associated with germline mutations, which predispose to a higher risk of developing cancer. Currently, the use of panels that identify susceptibility and/or association genes cancer has been increasingly used, both in clinical practice and in scientific research.

Objective To investigate genetic mutations in patients with a profile for hereditary cancer in individuals from a region of northeast Brazil, where there is a high frequency of endogenous and consanguineous marriages.

Methods A set of 17 genes (BRCA1, BRCA2, APC, TP53, PTEN, RET, VHL, RB1, CDKN2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, XPA, and XPC) associated with cancer and hereditary syndromes were analyzed. Fifteen patients with a hereditary cancer profile were evaluated.

Results The pathogenic variant found was c.1187G > A (p.Gly396Asp), rs36053993 in the MUTYH gene in a male patient diagnosed with melanoma at the age of 43 years and a family history for this tumor. This gene encodes an important enzyme related to DNA repair and has been associated with other types of cancer, this is the first report of an association with melanoma, the biological plausibility of this association is given once the MUTYH protein is expressed in the skin tissue and is responsible for repairing damage caused, for example, by sun exposure.

Conclusion The results of this study suggest that this mutation may be important for the hereditary predisposition to melanoma, but a broader investigation of this mutation is needed.
Impact of digital city competitiveness on total factor productivity in the commercial circulation industry: evidence from China’s emerging first-tier cities
Authors: Meng Tiantian , Yu Danni , Ye Ludi , Yahya M. H. , Zariyawati M. A.
Published: December 2023

In the age of rapid technological advancement, the proliferation of digital technologies has reshaped urban landscapes, affecting economic, social, and environmental dynamics. Urban digital transformation is more than just a technological innovation; it stands at the core of future urban competitive strategies. As this trend evolves, the commercial circulation industry is poised for significant opportunities. However, the academic exploration into the relationship between the level of urban digitalization and the total factor productivity of the commercial circulation industry remains limited. To address this gap, this study employs data from 15 emerging first-tier cities in China. Initially, a Digital City Competitiveness Index was established, with results indicating Hangzhou taking the lead, while other cities were categorized into distinct tiers. Utilizing a two-way fixed-effects model, the research then investigates the impact of digital city competitiveness on the total factor productivity of the commercial circulation industry. The findings suggest that digital city competitiveness significantly enhances the total factor productivity within this industry. Furthermore, the study examines the influences of various sub-dimensions of digital city competitiveness on total factor productivity. Notably, investments in urban information infrastructure emerge as the most pronounced positive factor, followed by industrial development, innovation, services, and governance. In contrast, the urban ecosystem dimension exerts a negative impact. This research fills an existing void in the literature concerning the relationship between digital city competitiveness and total factor productivity, offering profound insights into the interplay between digital city development and its economic benefits. In addition, the conclusions provide policy implications for decision-makers, highlighting the importance of bolstering urban information infrastructure, encouraging enterprises to innovate, fostering industrial clusters, enhancing urban service capabilities through digital means, elevating public participation, and emphasizing environmental conservation.
The born-digital in future digital scholarly editing and publishing
Authors: O’Sullivan James , Pidd Michael
Published: December 2023

Editorial scholarship is once again in a state of upheaval. Digital scholarly editing, for all it has achieved, has not accommodated the increasingly digital nature of cultural production and consumption. The theories and practices of digital scholarly editing need to better account for born-digital cultural materials like social media content, digital fiction, and video games. This paper discusses the state-of-the-art in digital scholarly editing, and advocates for future forms of digital scholarly editing and publishing suited to the born-digital.
The structural relations of self-control, empathy, interpersonal trust, friendship quality, and mental well-being among adolescents: a cross-national comparative study in China and Canada
Authors: Niu Jinpeng , Jin Chao , Meng Lingqi
Published: December 2023

The aim of the present study was to explore the structural relationships between self-control, empathy, interpersonal trust, friendship quality, and mental well-being among Chinese (N = 3595) and Canadian (N = 2056) adolescents. A structural equation modeling (SEM) approach was adopted by means of a multi-group analysis. Within the aggregate sample, empathy and interpersonal trust were shown to be related to mental well-being both directly and indirectly, with friendship quality as the mediating variable, whereas self-control merely had a direct effect on mental well-being. The multiple-group analysis revealed a series of discrepancies, showing that empathy had a significant impact on the mental well-being of Chinese but not Canadian adolescents. Furthermore, empathy exerted a significantly stronger effect on friendship quality for Chinese than for Canadian adolescents, whereas interpersonal trust had a significantly stronger impact on friendship quality among Canadian than among Chinese adolescents. The differences were discussed from a cross-cultural perspective concerning collectivism versus individualism. The measures employed in the present study are closely related to social and emotional skills; the findings therefore may point to benefits for both Chinese and Canadian adolescents in terms of enhancement of their cultural-specific social and emotional skills as well as their well-being.
Next generation of multispecific antibody engineering
Authors: Keri Daniel , Walker Matt , Singh Isha , Nishikawa Kyle , Garces Fernando
Published: December 2023

Multispecific antibodies recognize two or more epitopes located on the same or distinct targets. This added capability through protein design allows these man-made molecules to address unmet medical needs that are no longer possible with single targeting such as with monoclonal antibodies or cytokines alone. However, the approach to the development of these multispecific molecules has been met with numerous road bumps, which suggests that a new workflow for multispecific molecules is required. The investigation of the molecular basis that mediates the successful assembly of the building blocks into non-native quaternary structures will lead to the writing of a playbook for multispecifics. This is a must do if we are to design workflows that we can control and in turn predict success. Here, we reflect on the current state-of-the-art of therapeutic biologics and look at the building blocks, in terms of proteins, and tools that can be used to build the foundations of such a next-generation workflow.
Program for advancing supervisor skills among pharmacy technicians
Authors: MacKinnon Taylor , Schaeffler Kristen , Kent Stan , Clark John S
Published: December 2023

Purpose

This publication outlines the development and implementation of a leadership enhancement program for pharmacy technician supervisors at University of Michigan Health (UMH). The program aims to equip these supervisors with the skills and knowledge necessary to excel as leaders in the pharmacy field, addressing the pressing need for strong leaders in healthcare.

UMH recognized the need to cultivate effective leaders within its pharmacy department due to the impending shortage of pharmacy leaders and the rising demand for technicians and future pharmacists. To meet this need, a leadership enhancement program was introduced, offering flexibility and a comprehensive framework for enhancing the skills of pharmacy technician supervisors. The program covers annual, biennial, and flexible rotating topics and offers a structured monthly format for active participation. Additionally, the program utilizes a rigorous selection process for training resources and continuous quality improvement efforts to ensure effectiveness. Through developing leadership skills among technician supervisors, the organization aims to achieve tangible benefits, including decreased turnover rates and increased employee satisfaction.

Conclusion

The program for enhancing supervisor skills at UMH is a flexible and adaptable framework for leadership development in pharmacy. Its success in enhancing leadership skills for future pharmacy leaders is crucial in the evolving healthcare landscape and supports the growth of leaders in this domain. By acknowledging the value and expertise that pharmacy technicians bring, organizations can harness their potential and, in turn, benefit the entire healthcare system. This program’s principles are transferable to other organizations seeking to empower their employees with tools to thrive in new leadership roles, thus contributing to their growth and success.
An updated job-exposure matrix for occupational noise: development and validation
Authors: Sjöström Mattias , Lewné Marie , Alderling Magnus , Selander Jenny , Gustavsson Per
Published: December 2023

Objectives

The aim of this study was to create a quantitative job-exposure matrix (JEM) for noise including a large set of measurements for the Swedish workforce, a detailed exposure-level assessment, spanning over an extensive time period from 1970 to 2014.

Methods

The JEM was developed by 2 teams, each with an experienced occupational hygienist and an occupational safety engineer. Each pair assessed the exposure using measurements performed and reported by occupational hygienists, occupational safety engineers, or similar, from 1970 to 2014. The measurements included either the original LAeq(8h) measurements or an LAeq(8h) levels calculated from partial measurements of the working day, provided that the measurement targeted a regular task usually performed during a full workday. The collection of measurement reports was done in 2008 and 2012 by contacting clinics working in the area of occupational health or occupational safety engineers and their submitted reports were added to our own material. Noise exposure assessments were inserted at the appropriate time period for the relevant job family. The final matrix was developed in a consensus procedure and the validity was investigated by comparison of the 2 team’s individual results.

Results

The noise JEM contains 321 job families with information regarding occupational noise from 1970 to 2014. The time-period label has a 5-yr scale starting in 1970. The estimated average 8 h (TWA) noise level in decibels [dB(A)] for every job family and 5-yr period was coded as 1: <70 dB(A), 2: 70 to 74 dB(A), 3: 75 to 79 dB(A), 4: 80 to 84 dB(A) or 5: 85(+) dB(A). The validation showed no systematic difference in relative position and very high agreement in the ordering of paired ordinal classifications. The JEM has also successfully been applied in several epidemiological studies.

Conclusions

We present a JEM for occupational noise using Swedish data from 1970 to 2014 with a higher degree of sensitivity in assessed noise exposure compared with the previously existing version. Repeated application of the JEM, in epidemiological studies, has shown consistent results and contributed to yielding important findings.
Mechanisms of grapevine resilience to a vascular disease: investigating stem radial growth, xylem development and physiological acclimation
Authors: Dell’Acqua Ninon , Gambetta Gregory A , Delzon Sylvain , Ferrer Nathalie , Lamarque Laurent J , Saurin Nicolas , Theodore Pauline , Delmas Chloé E L
Published: December 2023

Background and Aims

Plant vascular diseases significantly impact crop yield worldwide. Esca is a vascular disease of grapevine found globally in vineyards which causes a loss of hydraulic conductance due to the occlusion of xylem vessels by tyloses. However, the integrated response of plant radial growth and physiology in maintaining xylem integrity in grapevine expressing esca symptoms remains poorly understood.

Methods

We investigated the interplay between variation in stem diameter, xylem anatomy, plant physiological response and hydraulic traits in two widespread esca-susceptible cultivars, ‘Sauvignon blanc’ and ‘Cabernet Sauvignon’. We used an original experimental design using naturally infected mature vines which were uprooted and transplanted into pots allowing for their study in a mini-lysimeter glasshouse phenotyping platform.

Key Results

Esca significantly altered the timing and sequence of stem growth periods in both cultivars, particularly the shrinkage phase following radial expansion. Symptomatic plants had a significantly higher density of occluded vessels and lower leaf and whole-plant gas exchange. Esca-symptomatic vines showed compensation mechanisms, producing numerous small functional xylem vessels later in development suggesting a maintenance of stem vascular cambium activity. Stabilization or late recovery of whole-plant stomatal conductance coincided with new healthy shoots at the top of the plant after esca symptoms plateaued.

Conclusions

Modified cropping practices, such as avoiding late-season topping, may enhance resilience in esca-symptomatic plants. These results highlight that integrating dendrometers, xylem anatomy and gas exchange provides insights into vascular pathogenesis and its effects on plant physiology.
Study of the genetic variability of durum wheat (Triticum durum Desf.) in the face of combined stress: water and heat
Authors: Chaouachi Latifa , Marín-Sanz Miriam , Barro Francisco , Karmous Chahine
Published: December 2023

The devastating effects and extent of abiotic stress on cereal production continue to increase globally, affecting food security in several countries, including Tunisia. Heat waves and the scarcity of rainfall strongly affect durum wheat yields. The present study aims to screen for tolerance to combined water and heat stresses in durum wheat at the juvenile stage. Three combined treatments were tested, namely: T0 (100% field capacity (FC) at 24 °C), T1 (50% FC at 30 °C), and T2 (25% FC at 35 °C). The screening was carried out based on morphological, physiological, and biochemical criteria. The results showed that the combined stress significantly affected all the measured parameters. The relative water content (RWC) decreased by 37.6% under T1 compared to T0. Quantum yield (Fv/m) and photosynthetic efficiency (Fv/0) decreased under severe combined stress (T2) by 37.15% and 37.22%, respectively. Under T2 stress, LT increased by 63.7%. A significant increase in osmoprotective solutes was also observed, including proline, which increased by 154.6% under T2. Correlation analyses of the combination of water and heat stress confirm that the traits RWC, chlorophyll b content, Fv/m, proline content, Fv/0 and leaf temperature can be used as reliable screening criteria for the two stresses combined. The principal component analysis highlighted that Aouija tolerates the two levels of stresses studied, while the genotypes Karim and Hmira are the most sensitive. The results show that the tolerance of durum wheat to combined water and heat stress involves several adaptation mechanisms proportional to the stress intensity.
The intracellular monoamine oxidase-A inhibitory activity and the protective effect of small hairtail-related peptides in nerve cells (SH-SY5Y)
Authors: Zhang Aiyuan , Yang Xiaoxue , Su Keying , Xie Jintao , Zhang Xuewu
Published: December 2023

This study was to investigate the inhibitory activity of small hairtail-related peptides (VFEVFW, LPNSLYQQ, LPNSLYQK, and FADAME) on intracellular monoamine oxidase-A (MAO-A) and their protective effects in a cell model. Specifically, the inhibition activity in SH-SY5Y cells indicated that VFEVFW and LPNSLYQK reduced ∼50% of MAO-A activity in cells, at 0.5 m m. The survival experiment demonstrated that the toxic effect of dexamethasone (DEX) on cells can be significantly alleviated in the presence of peptides, and these peptides can restore (>20%) the mitochondrial membrane potential of SH-SY5Y cells reduced by DEX. Circular dichroism displayed that peptides affected the secondary structure of MAO-A in a concentration-dependent manner. Finally, the real-time quantitative polymerase chain reaction assay revealed that the MAO-A inhibitory activity of the peptides was associated with the upregulation of brain derived neurotrophic factor/cAMP (Cyclic adenosine monophosphate) response element binding protein)/B-cell lymphoma-2 mRNA levels.
OBMeta: a comprehensive web server to analyze and validate gut microbial features and biomarkers for obesity-associated metabolic diseases
Authors: Xu Cuifang , Huang Jiating , Gao Yongqiang , Zhao Weixing , Shen Yiqi , Luo Feihong , Yu Gang , Zhu Feng , Ni Yan
Published: December 2023

Motivation

Gut dysbiosis is closely associated with obesity and related metabolic diseases including type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). The gut microbial features and biomarkers have been increasingly investigated in many studies, which require further validation due to the limited sample size and various confounding factors that may affect microbial compositions in a single study. So far, it lacks a comprehensive bioinformatics pipeline providing automated statistical analysis and integrating multiple independent studies for cross-validation simultaneously.

Results

OBMeta aims to streamline the standard metagenomics data analysis from diversity analysis, comparative analysis, and functional analysis to co-abundance network analysis. In addition, a curated database has been established with a total of 90 public research projects, covering three different phenotypes (Obesity, T2D, and NAFLD) and more than five different intervention strategies (exercise, diet, probiotics, medication, and surgery). With OBMeta, users can not only analyze their research projects but also search and match public datasets for cross-validation. Moreover, OBMeta provides cross-phenotype and cross-intervention-based advanced validation that maximally supports preliminary findings from an individual study. To summarize, OBMeta is a comprehensive web server to analyze and validate gut microbial features and biomarkers for obesity-associated metabolic diseases.

Availability and implementation

OBMeta is freely available at: http://obmeta.met-bioinformatics.cn/.
MMCL-CDR: enhancing cancer drug response prediction with multi-omics and morphology images contrastive representation learning
Authors: Li Yang , Guo Zihou , Gao Xin , Wang Guohua
Published: December 2023

Motivation

Cancer is a complex disease that results in a significant number of global fatalities. Treatment strategies can vary among patients, even if they have the same type of cancer. The application of precision medicine in cancer shows promise for treating different types of cancer, reducing healthcare expenses, and improving recovery rates. To achieve personalized cancer treatment, machine learning models have been developed to predict drug responses based on tumor and drug characteristics. However, current studies either focus on constructing homogeneous networks from single data source or heterogeneous networks from multiomics data. While multiomics data have shown potential in predicting drug responses in cancer cell lines, there is still a lack of research that effectively utilizes insights from different modalities. Furthermore, effectively utilizing the multimodal knowledge of cancer cell lines poses a challenge due to the heterogeneity inherent in these modalities.

Results

To address these challenges, we introduce MMCL-CDR (Multimodal Contrastive Learning for Cancer Drug Responses), a multimodal approach for cancer drug response prediction that integrates copy number variation, gene expression, morphology images of cell lines, and chemical structure of drugs. The objective of MMCL-CDR is to align cancer cell lines across different data modalities by learning cell line representations from omic and image data, and combined with structural drug representations to enhance the prediction of cancer drug responses (CDR). We have carried out comprehensive experiments and show that our model significantly outperforms other state-of-the-art methods in CDR prediction. The experimental results also prove that the model can learn more accurate cell line representation by integrating multiomics and morphological data from cell lines, thereby improving the accuracy of CDR prediction. In addition, the ablation study and qualitative analysis also confirm the effectiveness of each part of our proposed model. Last but not least, MMCL-CDR opens up a new dimension for cancer drug response prediction through multimodal contrastive learning, pioneering a novel approach that integrates multiomics and multimodal drug and cell line modeling.

Availability and implementation

MMCL-CDR is available at https://github.com/catly/MMCL-CDR.
CytoCopasi: a chemical systems biology target and drug discovery visual data analytics platform
Authors: Kaya Hikmet Emre , Naidoo Kevin J
Published: December 2023

Motivation

Target discovery and drug evaluation for diseases with complex mechanisms call for a streamlined chemical systems analysis platform. Currently available tools lack the emphasis on reaction kinetics, access to relevant databases, and algorithms to visualize perturbations on a chemical scale providing quantitative details as well streamlined visual data analytics functionality.

Results

CytoCopasi, a Maven-based application for Cytoscape that combines the chemical systems analysis features of COPASI with the visualization and database access tools of Cytoscape and its plugin applications has been developed. The diverse functionality of CytoCopasi through ab initio model construction, model construction via pathway and parameter databases KEGG and BRENDA is presented. The comparative systems biology visualization analysis toolset is illustrated through a drug competence study on the cancerous RAF/MEK/ERK pathway.

Availability and implementation

The COPASI files, simulation data, native libraries, and the manual are available on https://github.com/scientificomputing/CytoCopasi.
Dengue virus infection and neurological manifestations: an update
Authors: Fong Si-Lei , Wong Kum-Thong , Tan Chong-Tin
Published: December 2023

Dengue virus is a flavivirus transmitted by the mosquitoes, Aedes aegypti and Aedes albopictus. Dengue infection by all four serotypes (DEN 1 to 4) is endemic globally in regions with tropical and subtropical climates, with an estimated 100–400 million infections annually. Among those hospitalized, the mortality is about 1%. Neurological involvement has been reported to be about 5%. The spectrum of neurological manifestations spans both the peripheral and central nervous systems. These manifestations could possibly be categorized into those directly related to dengue infection, i.e. acute and chronic encephalitis, indirect complications leading to dengue encephalopathy, and post-infectious syndrome due to immune-mediated reactions, and manifestations with uncertain mechanisms, such as acute transverse myelitis, acute cerebellitis and myositis.

The rising trend in global dengue incidence calls for attention to a more explicit definition of each neurological manifestation for more accurate epidemiological data. The actual global burden of dengue infection with neurological manifestation is essential for future planning and execution of strategies, especially in the development of effective antivirals and vaccines against the dengue virus.

In this article, we discuss the recent findings of different spectrums of neurological manifestations in dengue infection and provide an update on antiviral and vaccine development and their challenges.
Asbestos burden in lungs of mesothelioma patients with pleural plaques, lung fibrosis and/or ferruginous bodies at histology: a postmortem SEM-EDS study
Authors: Visonà S D , Bertoglio B , Capella S , Belluso E , Austoni B , Colosio C , Kurzhunbaeva Z , Ivic-Pavlicic T , Taioli E
Published: December 2023

The causal attribution of asbestos-related diseases to past asbestos exposures is of crucial importance in clinical and legal contexts. Often this evaluation is made based on the history of exposure, but this method presents important limitations. To assess past asbestos exposure, pleural plaques (PP), lung fibrosis and histological evidence of ferruginous bodies (FB) can be used in combination with anamnestic data. However, such markers have never been associated with a threshold value of inhaled asbestos. With this study we attempted to shed light on the dose–response relationship of PP, lung fibrosis and FBs, investigating if their prevalence in exposed individuals who died from malignant mesothelioma (MM) is related to the concentration of asbestos in lungs assessed using scanning electron microscopy equipped with energy dispersive spectroscopy. Moreover, we estimated the values of asbestos concentration in lungs associated with PP, lung fibrosis and FB. Lung fibrosis showed a significant positive relationship with asbestos lung content, whereas PP and FB did not. We identified, for the first time, critical lung concentrations of asbestos related to the presence of PP, lung fibrosis and FB at histology (respectively, 19 800, 26 400 and 27 400 fibers per gram of dry weight), that were all well-below the background levels of asbestos identified in our laboratory. Such data suggest that PP, lung fibrosis and FB at histology should be used with caution in the causal attribution of MM to past asbestos exposures, while evaluation of amphibole lung content using analytical electron microscopy should be preferred.
Sunburn, sunbeds and melanoma skin cancer: a story behind the statistics
Authors: Fleming Sarah , Dolan Michelle , Greenwood Michelle , Blake Carmel , Tobin Anne-Marie , Connolly Maureen
Published: December 2023

Our patient’s story highlights the ongoing psychological impact the diagnosis of skin cancer has on patients.