bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Indicators of Learning Disabilities in Children with Developmental Language Disorder Compared to Their Typically Developing Peers
Authors: Yaşa İbrahim Can , Çiyiltepe Müge Müzeyyen
Published: August 2024

Developmental language disorder (DLD) is a language deficit affecting approximately 7% of the general population and does not associate with any hearing impairment, neurological damage, or mental disorder. In DLD, the complications arise over time due to the learning difficulties experienced, which causes eventual cognitive delay compared to peers. Therefore, early diagnosis is important in children with DLD. In this study, the objective was to screen for early signs of learning disability in children aged 4 to 6 years with DLD. The study included 30 normal developing children and 26 children with DLD. The children with normal development comprised 17 boys and 13 girls, while the group of children with DLD included 16 boys and 10 girls. Learning disability was evaluated using the Learning Disability Early Symptoms Screening Scale (LDESSS) and Test of Early Literacy (TEL). Children with DLD scored higher on all subscales of LDESSS and lower on all subscales of TEL than the normal developing group ( p < .001). According to LDESSS and TEL scores, the risk of learning disability in children with DLD was significantly higher than the normal developing group. In addition, gender had no significant association in terms of learning disability. Since the risk of learning disabilities in children with DLD is higher than normal developing peers, early diagnosis and early therapy is recommended to prevent academic and social problems in the future.
How Product Standards Influence Tea Exports? Empirical Evidence from India
Authors: Pradhani Manash Roy , Chakraborty Debashis , Ghosh Triptendu Prakash
Published: August 2024

India has witnessed a declining trend in tea exports in the recent period, which can partly be attributed to competition from exporters (e.g., Kenya and Sri Lanka) enjoying price advantages over the Indian varieties. However, although after the inception of the World Trade Organization (WTO) in 1995, the tariff barriers on Indian tea exports have come down across developed partners, the incidence of non-tariff barriers (NTBs) has emerged as a challenge in many destinations, with a possible dampening effect on exports. The present analysis attempts to analyse whether the imposition of product standard related measures, particularly sanitary and phytosanitary (SPS) and Technical Barriers to Trade (TBT) interventions, may have negatively influenced Indian tea exports over the period 1996–2021. Rather than considering the mere presence of SPS–TBT standards in major partner countries, their potential impacts on Indian tea exports have been determined by analysing the stringency levels of the corresponding notifications submitted to the WTO. The constructed stringency patterns are then incorporated into the Poisson pseudo maximum likelihood estimation models. The observed negative influence of standard-related measures in partner countries on Indian tea exports calls for policy interventions to enable the sector to better ensure compliance in the future.
Patient Preferences for Graft Selection in Anterior Cruciate Ligament Reconstruction
Authors: Pearsall Christian , Chen Aaron Z. , Abdelaziz Abed , Saltzman Bryan M. , Piasecki Dana P. , Popkin Charles A. , Redler Lauren H. , Levine William N. , Ahmad Christopher S. , Trofa David P.
Published: August 2024

Background:

Selecting an appropriate graft for anterior cruciate ligament (ACL) reconstruction requires consideration of a patient's preferences, goals, age, and physical demands alongside the risks and benefits of each graft choice.

Purpose:

To determine the most popular ACL reconstruction grafts among patients and the most important factors influencing their decisions.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

Patients undergoing ACL reconstruction between October 2022 and April 2023 completed a survey either before (nonconsult group) or after (consult group) speaking with their surgeon, who provided an evidence-based description of the pros and cons of an allograft and the following autografts: bone-patellar tendon-bone (BPTB), hamstring tendon (HT), and quadriceps tendon (QT). Patient characteristics, graft choice, information influencing their graft choice, and surgeon recommendation were collected and compared between the groups.

Results:

Among the 100 included patients, 59.0% were male, and the mean age was 28.3 ± 10.4 years. The most popular grafts were the BPTB (56.0%), followed by the QT (29.0%), HT (8.0%), and allograft (7.0%). No significant difference was observed in the graft selection between the consult group (n = 60; BPTB, 46.7%; QT, 38.3%; HT, 8.3%; allograft, 6.7%) and nonconsult group (n = 40; BPTB, 70.0%; QT, 15.0%; HT, 7.5%; allograft, 7.5%) ( P = .0757). In the consult group, 81.7% of patients selected the graft recommended to them by their surgeon. The top 2 graft selection reasons were usage in professional athletes and failure rates, while the top 2 ACL surgery concerns were returning to their desired level of athletics and graft failure risk. Among the 93 patients who researched their ACL graft options before their visit, the most popular information source was some form of media (72.0% [67/93]).

Conclusion:

The study findings underscore the importance of patient preference and surgeon recommendation in a patient's graft selection and highlight the need to be cognizant of the information sources available to patients when researching their graft options.
Incidence of Osteoarthritis Between ACL Reconstruction With Different Graft Types and Between ACL Reconstruction and Repair: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Vendrig Tom , Keizer Michèle N.J. , Brouwer Reinoud W. , Hoogeslag Roy A.G.
Published: August 2024

Background:

Variation in stiffness, fixation methods, and donor-site morbidity after anterior cruciate ligament reconstruction (ACLR) with different graft types and with anterior cruciate ligament suture repair (ACLSR) can lead to differences in dynamic knee laxity and consequent differences in posttraumatic osteoarthritis (PTOA) development.

Purpose:

To compare the incidence of PTOA between different graft types used for primary ACLR and between primary ACLR and ACLSR. It was hypothesized that the incidence of PTOA would vary between ACLR with different autografts and allografts and between ACLR and ACLSR.

Study Design:

Systematic review; Level of evidence, 1.

Methods:

A search of the literature was performed to identify all randomized controlled trials (RCTs) comparing radiographic evidence of PTOA after ACLR between different graft types—hamstring tendon (HT) autograft, bone-patellar tendon-bone (BPTB) autograft, quadriceps tendon autograft, and allograft—and between ACLR and ACLSR. The minimum follow-up was 2 years. Study quality was assessed using the modified Coleman Methodology Score. A meta-analysis was performed to determine whether there was a difference in the incidence of PTOA between the different graft types and between ACLR and ACLSR.

Results:

Eleven randomized controlled trials were included in the meta-analysis—HT: 440 patients (mean follow-up, 9.7 years); BPTB: 307 patients (mean follow-up, 11.8 years); allograft: 246 patients (mean follow-up, 5 years); ACLSR, 22 patients (5 years). No study reporting the incidence after ACLR with quadriceps tendon was included. The study quality ranged from 70 to 88. The meta-analysis indicated no significant difference in the incidence of PTOA between graft types used for ACLR and between ACLR and ACLSR (risk ratios: HT vs BPTB, 1.05; HT vs allograft, 0.81; BPTB vs allograft, 0.82; HT vs ACLSR, not estimable [ P > .05 for all]). The combined number of patients with PTOA in all studies per graft type showed that patients who underwent ACLR with a BPTB autograft had the highest percentage of PTOA (HT, 23.4%; BPTB, 29.6%; allograft, 8.1%; ACLSR, 0%). However, excluding studies with a follow-up <5 years resulted in similar outcomes for patients with an HT autograft and a BPTB autograft.

Conclusion:

This meta-analysis reported no difference in the incidence of PTOA between graft types used for ACLR and between ACLR and ACLSR. More research is necessary to make a reliable conclusion about which technique is associated with the lowest incidence of PTOA after ACL surgery.
The Role of Humeral Torsion on Glenohumeral Rotation in Injured Baseball Players
Authors: Entler Kalie , Kruseman J. Kaylin , Kennedy Sean M. , Conway John E. , Reyes Griffin J. , Garrison J. Craig , Bailey Lane B. , Myers Natalie L.
Published: August 2024

Background:

Differences in rotational range of motion (ROM) compared to humeral retrotorsion (HRT)–corrected rotational ROM exist in healthy baseball athletes, but it is unclear whether these differences exist in a pathological population.

Purpose/Hypothesis:

The purpose of this study was to determine if there are disparities between objectively measured differences in ROM and HRT-corrected deficits in injured baseball players. It was hypothesized that disparities would exist between (1) the side-to-side difference in glenohumeral external rotation (GER) and the HRT-corrected glenohumeral external rotation deficit (GERD) and (2) the side-to-side difference in glenohumeral internal rotation (GIR) and the HRT-corrected glenohumeral internal rotation deficit (GIRD).

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

Data from 172 baseball players with shoulder or elbow injuries (45 shoulder, 127 elbow) were reviewed in July 2023. GER and GIR were measured on the injured and noninjured sides of all players, and diagnostic ultrasound was used to measure HRT. Dependent t tests were run to compare the side-to side differences in GER and GIR with the HRT-corrected GERD and GIRD, respectively.

Results:

In the players with a shoulder injury, there was a significant disparity between the side-to-side difference in GER and the HRT-corrected GERD (2°± 14° vs −13°± 15°, respectively) and between the side-to-side difference in GIR and the HRT-corrected GIRD (–14°± 8° vs 2°± 9°, respectively) ( P < .001 for both). Similarly, players with an elbow injury had significant disparities between the side-to-side difference in GER and the HRT-corrected GERD (6°± 9° vs −10°± 9°, respectively) and between the side-to-side difference in GIR and the HRT-corrected GIRD (–12°± 8° vs 4°± 10°, respectively) ( P < .001 for both).

Conclusion:

The results supported our hypothesis that there were disparities between objectively measured differences in GER and GIR compared with the HRT-corrected GERD and GIRD in injured baseball players. Consideration must be given to osseous adaptations that occur at the glenohumeral joint when evaluating and treating this population.
Brain mechanisms of temporal processing in impulsivity: Relevance to attention-deficit hyperactivity disorder
Authors: White Eleanor , Dalley Jeffrey W.
Published: August 2024

In this article, we critique the hypothesis that different varieties of impulsivity, including impulsiveness present in attention-deficit hyperactivity disorder, encompass an accelerated perception of time. This conceptualisation provides insights into how individuals with attention-deficit hyperactivity disorder have the capacity to maximise cognitive capabilities by more closely aligning themselves with appropriate environmental contexts (e.g. fast paced tasks that prevent boredom). We discuss the evidence for altered time perception in attention-deficit hyperactivity disorder alongside putative underlying neurobiological substrates, including a distributed brain network mediating time perception over multiple timescales. In particular, we explore the importance of temporal representations across the brain for time perception and symptom manifestation in attention-deficit hyperactivity disorder, including a prominent role of the hippocampus and other temporal lobe regions. We also reflect on how abnormalities in the perception of time may be relevant for understanding the aetiology of attention-deficit hyperactivity disorder and mechanism of action of existing medications.
Phenytoin relieves acute exacerbations of trigeminal neuralgia: Results of a retrospective case series
Authors: Kolakowski Lukasz , Pohl Heiko , Kleinsorge Marie Therese , Wegener Susanne
Published: August 2024

Introduction

The management of acute exacerbations of trigeminal neuralgia remains a major clinical challenge due to the limited availability of clinical evidence. This retrospective case series aims to evaluate the effectiveness and safety of intravenous phenytoin in the treatment of these exacerbations.

Methods

We retrospectively analyzed the outcome of patients treated with intravenous phenytoin for acute exacerbations of trigeminal neuralgia at the University Hospital Zurich between January 2016 and December 2023. Statistical analyses were performed to assess the associations of patient and disease characteristics with phenytoin response.

Results

In our sample of 45 cases, treatment with phenytoin resulted in a significant or complete relief in 30 cases (66.7%), while 11 (24.4%) experienced slight relief and 4 (8.9%) none. Patient or disease characteristics were not associated with treatment response. Side effects were rare, with skin itching occurring in only one case.

Conclusion

This retrospective case series demonstrates, that phenytoin is a safe and effective treatment for acute exacerbations of trigeminal neuralgia. However, larger prospective studies are needed.
Restrictions on Chinese SOE Investments for Data Security Reasons: The Case of Australia
Authors: Gu Tianqi
Published: August 2024

In the digital age, the proliferation of investments made by Chinese state-owned enterprises (SOEs) has raised concerns among host countries about the risks that the investments could provide the Chinese government access to sensitive data involved in the target businesses, posing threats to their national security. Consequently, countries with sophisticated foreign investment screening (FIS) regimes, such as Australia, have imposed entry restrictions on Chinese SOE foreign direct investment (FDI) on the grounds of data security concerns. This article takes Australia as an example to investigate whether this concern has become a ‘panacea’ to justify any restrictions imposed by host states on Chinese SOE FDI in the digital age. Through in-depth examinations of Australia's reformed FIS regime and its application to Chinese SOE investments, this article demonstrates that data security has increasingly become a preferred justification for imposing restrictions on Chinese SOE investments. It argues that the data security justification is legitimate because of Chinese SOEs’ strong political ties, which have been significantly strengthened in China's ongoing SOE reforms, as well as China's prominent policy emphasis on data protection in recent years. However, measures should be taken to mitigate data security becoming a ‘minefield’ impeding the restoration of Australia–China investment relations.
A Sociology of Plasma Proteins – A Technocrat's Perspective
Authors: Farrugia Albert
Published: August 2024

This commentary addresses the article “Toward a Sociology of Plasma Products” by Holloway and Grundy in this issue of the International Journal of Social Determinants of Health and Health Services. The program of research proposed by the authors positioning the medico-industrial field of plasma products within a sociological context is supported, this being an endeavor which has not been attempted previously. I seek to augment Holloway and Grundy's proposed approach through some additional insights which are the result of over forty years of personal commitment in the field. Holloway and Grundy's proposed areas of engagement involving the products, the recipients, the donors and the governance of the systems binding these together is widened through an examination of additional technological factors that have shaped the field. These factors include the influence of the medical industry, the role of patient groups, the continuing controversy on the sourcing of plasma raw material, and the roles of different governance models. Converging these factors with Holloway and Grundy's proposed program should enhance its capacity to develop a framework for understanding the dynamics within this complex and unique sector. The concepts developed in both articles will assist stakeholders to develop a societal framework for the provision of these essential medicines.
A systematic review of procedural and sampling techniques for cryobiopsy in interstitial lung disease
Authors: Lachowicz Julia A. , Smallwood Natasha E. , Prasad Jyotika D. , Patel Purab , Voutier Catherine , Khor Yet H. , Steinfort Daniel P.
Published: August 2024

Background

Transbronchial lung cryobiopsy (TBLC) is an alternative to surgical lung biopsy for histopathological evaluation of unclassifiable interstitial lung disease (ILD) or ILD diagnosed with low confidence. This meta-analysis synthesised current literature regarding cryobiopsy diagnostic performance and safety, focusing on procedural and sampling techniques.

Methods

Medline and Embase were searched on 11 April 2022. Studies included adults with unclassifiable ILD, reporting diagnostic yield, complications and methodological techniques of TBLC. Meta-analyses were performed for diagnostic yield, pneumothorax and bleeding. Subgroup analyses and meta-regression assessed methodological variables. PROSPERO registration: CRD42022312386.

Results

70 studies were included with 6183 participants. Diagnostic yield of TBLC was 81% (95% CI 79–83%, I2=97%), with better yield being observed with general anaesthesia (p=0.007), ILD multidisciplinary meeting prior to cryobiopsy (p=0.02), 2.4 mm cryoprobe (p=0.04), higher mean forced vital capacity (p=0.046) and higher mean diffusing capacity for carbon monoxide (p=0.023). Pneumothorax rate was 5% (95% CI 4–5%, I2=91%), with higher rates associated with a 2.4 mm cryoprobe (p<0.00001), routine post-procedure imaging (p<0.00001), multiple lobe sampling (p<0.0001), reduced mean diffusing capacity for carbon monoxide (p=0.028) and general anaesthesia (p=0.05). Moderate-to-severe bleeding rate was 12% (11–14%, I2=95%) and higher rates were associated with a 2.4 mm cryoprobe (p=0.001) and bleeding score selection (p=0.04).

Interpretation

Patient characteristics and modifiable factors, including procedural methods and anaesthetic techniques, impacted diagnostic yield and safety outcomes of TBLC in people with unclassifiable ILD and contributed to heterogeneity of clinical outcomes. These variables should be considered for individualised clinical decision making and guideline development and warrant routine reporting in future research.
Integrated behavioral health implementation and chronic disease management inequities: an exploratory study of statewide data
Authors: Buchanan Gretchen J. R. , Berge Jerica M. , F. Piehler Timothy
Published: August 2024

Background

People with diabetes, vascular disease, and asthma often struggle to maintain stability in their chronic health conditions, particularly those in rural areas, living in poverty, or racially or ethnically minoritized populations. These groups can experience inequities in healthcare, where one group of people has fewer or lower-quality resources than others. Integrating behavioral healthcare services into primary care holds promise in helping the primary care team better manage patients’ conditions, but it involves changing the way care is delivered in a clinic in multiple ways. Some clinics are more successful than others in fully integrating behavioral health models as shown by previous research conducted by our team identifying four patterns of implementation: Low, Structural, Partial, and Strong. Little is known about how this variation in integration may be related to chronic disease management and if IBH could be a strategy to reduce healthcare inequities. This study explores potential relationships between IBH implementation variation and chronic disease management in the context of healthcare inequities.

Methods

Building on a previously published latent class analysis of 102 primary care clinics in Minnesota, we used multiple regression to establish relationships between IBH latent class and healthcare inequities in chronic disease management, and then structural equation modeling to examine how IBH latent class may moderate those healthcare inequities.

Results

Contrary to our hypotheses, and demonstrating the complexity of the research question, clinics with better chronic disease management were more likely to be Low IBH rather than any other level of integration. Strong and Structural IBH clinics demonstrated better chronic disease management as race in the clinic’s location became more White.

Conclusions

IBH may result in improved care, though it may not be sufficient to resolve healthcare inequities; it appears that IBH may be more effective when fewer social determinants of health are present. Clinics with Low IBH may not be motivated to engage in this practice change for chronic disease management and may need to be provided other reasons to do so. Larger systemic and policy changes are likely required that specifically target the mechanisms of healthcare inequities.
Social disparities in access and quality of consultation in outpatient care in Germany
Authors: von dem Knesebeck Olaf , Lüdecke Daniel , Klein Jens
Published: August 2024

Background

Overall, research on social determinants of access and quality of outpatient care in Germany is scarce. Therefore, social disparities (according to sex, age, income, migration background, and health insurance) in perceived access and quality of consultation in outpatient care (primary care physicians and specialists) in Germany were explored in this study.

Methods

Analyses made use of a cross-sectional online survey. An adult population sample was randomly drawn from a panel which was recruited offline (N = 2,201). Perceived access was assessed by waiting time for an appointment (in days) and travel time to the practice (in minutes), while quality of consultation was measured by consultation time (in minutes) and quality of communication (scale of four items, Cronbach’s Alpha 0.89).

Results

In terms of primary care, perceived access and quality of consultation was worse among women compared to men. Estimated consultation time was shorter among people with statutory health insurance compared to privately insured respondents. Regarding specialist care, people aged 60 years and older reported shorter waiting times and better quality of communication. Lower income groups reported lower quality of communication, while perceived access and quality of consultation was worse among respondents with a statutory health insurance. Variances explained by the social characteristics ranged between 1% and 4% for perceived access and between 3% and 7% for quality of consultation.

Conclusion

We found social disparities in perceived access and quality of consultation in outpatient care in Germany. Such disparities in access may indicate structural discrimination, while disparities in quality of consultation may point to interpersonal discrimination in health care.
Analysis of intracellular communication reveals consistent gene changes associated with early-stage acne skin
Authors: Deng Min , Odhiambo Woodvine O. , Qin Min , To Thao Tam , Brewer Gregory M. , Kheshvadjian Alexander R. , Cheng Carol , Agak George W.
Published: August 2024

A comprehensive understanding of the intricate cellular and molecular changes governing the complex interactions between cells within acne lesions is currently lacking. Herein, we analyzed early papules from six subjects with active acne vulgaris, utilizing single-cell and high-resolution spatial RNA sequencing. We observed significant changes in signaling pathways across seven different cell types when comparing lesional skin samples (LSS) to healthy skin samples (HSS). Using CellChat, we constructed an atlas of signaling pathways for the HSS, identifying key signal distributions and cell-specific genes within individual clusters. Further, our comparative analysis revealed changes in 49 signaling pathways across all cell clusters in the LSS— 4 exhibited decreased activity, whereas 45 were upregulated, suggesting that acne significantly alters cellular dynamics. We identified ten molecules, including GRN, IL-13RA1 and SDC1 that were consistently altered in all donors. Subsequently, we focused on the function of GRN and IL-13RA1 in TREM2 macrophages and keratinocytes as these cells participate in inflammation and hyperkeratinization in the early stages of acne development. We evaluated their function in TREM2 macrophages and the HaCaT cell line. We found that GRN increased the expression of proinflammatory cytokines and chemokines, including IL-18, CCL5, and CXCL2 in TREM2 macrophages. Additionally, the activation of IL-13RA1 by IL-13 in HaCaT cells promoted the dysregulation of genes associated with hyperkeratinization, including KRT17, KRT16, and FLG. These findings suggest that modulating the GRN-SORT1 and IL-13-IL-13RA1 signaling pathways could be a promising approach for developing new acne treatments.
Validation of an AI-based solution for breast cancer risk stratification using routine digital histopathology images
Authors: Sharma Abhinav , Lövgren Sandy Kang , Eriksson Kajsa Ledesma , Wang Yinxi , Robertson Stephanie , Hartman Johan , Rantalainen Mattias
Published: August 2024

Background

Stratipath Breast is a CE-IVD marked artificial intelligence-based solution for prognostic risk stratification of breast cancer patients into high- and low-risk groups, using haematoxylin and eosin (H&E)-stained histopathology whole slide images (WSIs). In this validation study, we assessed the prognostic performance of Stratipath Breast in two independent breast cancer cohorts.

Methods

This retrospective multi-site validation study included 2719 patients with primary breast cancer from two Swedish hospitals. The Stratipath Breast tool was applied to stratify patients based on digitised WSIs of the diagnostic H&E-stained tissue sections from surgically resected tumours. The prognostic performance was evaluated using time-to-event analysis by multivariable Cox Proportional Hazards analysis with progression-free survival (PFS) as the primary endpoint.

Results

In the clinically relevant oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative patient subgroup, the estimated hazard ratio (HR) associated with PFS between low- and high-risk groups was 2.76 (95% CI: 1.63–4.66, p-value < 0.001) after adjusting for established risk factors. In the ER+/HER2- Nottingham histological grade (NHG) 2 subgroup, the HR was 2.20 (95% CI: 1.22–3.98, p-value = 0.009) between low- and high-risk groups.

Conclusion

The results indicate an independent prognostic value of Stratipath Breast among all breast cancer patients, as well as in the clinically relevant ER+/HER2- subgroup and the NHG2/ER+/HER2- subgroup. Improved risk stratification of intermediate-risk ER+/HER2- breast cancers provides information relevant for treatment decisions of adjuvant chemotherapy and has the potential to reduce both under- and overtreatment. Image-based risk stratification provides the added benefit of short lead times and substantially lower cost compared to molecular diagnostics and therefore has the potential to reach broader patient groups.
Open total talus dislocation without concomitant malleoli fracture: a case report
Authors: Lamichhane Sameer , Maharjan Rajiv , Thapa Pramesh , Dhakal Binit , Dhungana Amit
Published: August 2024

Background

Total talus dislocation without ankle (malleoli) fracture is a very rare injury with prevalence of only 0.06% of all dislocations and only 2% of talar injuries, and are usually associated with common complications such as infection, avascular necrosis, and posttraumatic arthritis. The treatment usually involves debridement, reduction, stabilization of the ankle joint, and primary or secondary closure of the wound.

Case presentation

We present the case of a 40-year-old South Asian woman who was involved in an accident. She was rushed to our hospital, whereby subsequent examination revealed an open total talus dislocation with the talus being exposed in its entirety from a contaminated wound in the medial side. Furthermore, radiograph confirmed total talus dislocation without concomitant malleoli fracture. She was immediately taken to the operating theater whereby debridement and immediate reduction was performed under anesthesia, and the ankle was stabilized with external fixator for about 6 weeks. She is now able to bear weight on the affected ankle with minimal tolerable pain and has normal range of motion of the ankle.

Conclusions

Open total talus dislocation without concomitant malleoli fracture is a rare injury. Reduction of the talus in combination with complete wound debridement potentially successfully avoids infection, provides early revascularization preventing avascular necrosis, and preserves the normal ankle anatomy.
Metis: a python-based user interface to collect expert feedback for generative chemistry models
Authors: Menke Janosch , Nahal Yasmine , Bjerrum Esben Jannik , Kabeshov Mikhail , Kaski Samuel , Engkvist Ola
Published: August 2024

One challenge that current de novo drug design models face is a disparity between the user’s expectations and the actual output of the model in practical applications. Tailoring models to better align with chemists’ implicit knowledge, expectation and preferences is key to overcoming this obstacle effectively. While interest in preference-based and human-in-the-loop machine learning in chemistry is continuously increasing, no tool currently exists that enables the collection of standardized and chemistry-specific feedback. is a Python-based open-source graphical user interface (GUI), designed to solve this and enable the collection of chemists’ detailed feedback on molecular structures. The GUI enables chemists to explore and evaluate molecules, offering a user-friendly interface for annotating preferences and specifying desired or undesired structural features. By providing chemists the opportunity to give detailed feedback, allows researchers to capture more efficiently the chemist’s implicit knowledge and preferences. This knowledge is crucial to align the chemist’s idea with the de novo design agents. The GUI aims to enhance this collaboration between the human and the “machine” by providing an intuitive platform where chemists can interactively provide feedback on molecular structures, aiding in preference learning and refining de novo design strategies. integrates with the existing de novo framework REINVENT, creating a closed-loop system where human expertise can continuously inform and refine the generative models.

Scientific contribution

We introduce a novel Graphical User Interface, that allows chemists/researchers to give detailed feedback on substructures and properties of small molecules. This tool can be used to learn the preferences of chemists in order to align de novo drug design models with the chemist’s ideas. The GUI can be customized to fit different needs and projects and enables direct integration into de novo REINVENT runs. We believe that can facilitate the discussion and development of novel ways to integrate human feedback that goes beyond binary decisions of liking or disliking a molecule.
Transient motion classification and segment analysis of diffusive trajectories of G proteins and coupled-receptors in a living cell
Authors: Stanislavsky Aleksander A. , Weron Aleksander
Published: August 2024

The molecular movement in single particle tracking (SPT) experiments shows a crucial role of diffusion in many biological processes such as signaling, cellular organization, transport mechanisms, and more. The SPT analysis detects not only classical Brownian motion but diffusion with other features. These include directed diffusion and confined motion. The behavior remains a challenging problem for several reasons. Due to the action of many physical processes, random trajectories of cellular molecules are segmented in different diffusive modes. Often their study requires sophisticated algorithms for the analysis of statistical properties. In this paper we consider the segment analysis for trajectories of G proteins and coupled-receptors in living cells. Their movement is often transient and switches among free diffusion, confined diffusion, directed diffusion, and immobility. Moreover, the confined segments can have both Gaussian and non-Gaussian statistics. The types of alternation of diffusive modes along the trajectories of G proteins and coupled-receptors are analyzed.
TRIM5 inhibits the replication of Senecavirus A by promoting the RIG-I-mediated type I interferon antiviral response
Authors: Li Huizi , Xie Zhenxin , Lei Xiaoling , Chen Ming , Zheng Tingting , Lin Cunhao , Ning Zhangyong
Published: August 2024

Senecavirus A (SVA) is an emerging virus that poses a threat to swine herds worldwide. To date, the role of tripartite motif 5 (TRIM5) in the replication of viruses has not been evaluated. Here, TRIM5 was reported to inhibit SVA replication by promoting the type I interferon (IFN) antiviral response mediated by retinoic acid-inducible gene I (RIG-I). TRIM5 expression was significantly upregulated in SVA-infected cells, and TRIM5 overexpression inhibited viral replication and promoted IFN-α, IFN-β, interleukin-1beta (IL-1β), IL-6, and IL-18 expression. Conversely, interfering with the expression of TRIM5 had the opposite effect. Viral adsorption and entry assays showed that TRIM5 did not affect the adsorption of SVA but inhibited its entry. In addition, TRIM5 promoted the expression of RIG-I and RIG-I-mediated IFNs and proinflammatory cytokines, and this effect was also proven by inhibiting the expression of TRIM5. These findings expand the scope of knowledge on host factors inhibiting the replication of SVA and indicate that targeting TRIM5 may aid in the development of new agents against SVA.
Understanding the role of mobility in the recorded levels of violent crimes during COVID-19 pandemic: a case study of Tamil Nadu, India
Authors: Paramasivan Kandaswamy , Jaiswal Saish , Subburaj Rahul , Sudarsanam Nandan
Published: August 2024

Purpose/Goal

This research investigates the potential link between mobility and violent crimes in Tamil Nadu, India, using an empirical study centred on the COVID-19 pandemic waves (2020–2022). The goal is to understand how these events influenced crime, employing a counterfactual approach.

Methods

The study employs the XGBoost algorithm to forecast counterfactual events across different timeframes with varying levels of mobility. The mobility data sources include historical bus and passenger records spanning a decade, along with Google Community Mobility Reports added during the pandemic phases. The foundation for crime analysis is built upon the univariate time series of violent crimes reported as First Information Reports from 2010 to 2022.

Findings

Results indicate a significant correlation between mobility and violent crimes when mobility drops below a specific threshold. However, no such correlation is observed when mobility is above this threshold during the non-pandemic periods. The COVID-19 pandemic had a major impact on people’s and vehicular mobility, especially during the complete lockdown periods of the first two waves, and also affected crime rates.

Conclusions

The decrease in recorded incidents could also be attributed to fewer criminal opportunities. Additionally, this could be due to unfavourable situational factors, such as victims’ limited access to appropriate health and law enforcement agencies to report crimes. Furthermore, frontline services were busy with pandemic-related commitments, which could have contributed to a lack of crime registration even when crimes were committed.
Field measurements of turbulent mixing south of the Lombok Strait, Indonesia
Authors: Susanto R. Dwi , Wei Zexun , Santoso Priyadi Dwi , Wang Guanlin , Fadli Muhammad , Li Shujiang , Agustiadi Teguh , Xu Tengfei , Priyono Bayu , Li Ying , Fang Guohong
Published: August 2024

The Indonesian seas, with their complex passages and vigorous mixing, constitute the only route and are critical in regulating Pacific–Indian Ocean interchange, air–sea interaction, and global climate events. Previous research employing remote sensing and numerical simulations strongly suggested that this mixing is tidally driven and localized in narrow channels and straits, with only a few direct observations to validate it. The current study offers the first comprehensive temporal microstructure observations in the south of Lombok Strait with a radius of 0.05° and centered on 115.54oE and 9.02oS. Fifteen days of tidal mixing observations measured potential temperature and density, salinity, and turbulent energy dissipation rate. The results revealed significant mixing and verified the remotely sensed technique. The south Lombok temporal and depth averaged of the turbulent kinetic energy dissipation rate, and the diapycnal diffusivity from 20 to 250 m are $$\varepsilon$$
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K
ρ

 = (9.2 ± 0.55) × 10–6 m2s–1] (Alford et al. Geophys Res Lett 26:2741–2744, 1999) or the “open ocean” $$K\rho$$

K
ρ

= 0.03 × 10–4 m2s−1 within 2° of the equator to (0.4–0.5) × 10–4 m2s−1 at 50°–70° (Kunze et al. J Phys Oceanogr 36:1553–1576, 2006). Therefore, nonlinear interactions between internal tides, tidally induced mixing, and ITF plays a critical role regulating water mass transformation and have strong implications to longer-term variations and change of Pacific–Indian Ocean water circulation and climate.
Surgical approach for a refractory enterocutaneous fistula by combining laparoscopic surgery and a planned open conversion: a case report
Authors: Hasegawa Makoto , Ogino Takayuki , Sekido Yuki , Takeda Mitsunobu , Hata Tsuyoshi , Hamabe Atsushi , Miyoshi Norikatsu , Uemura Mamoru , Doki Yuichiro , Eguchi Hidetoshi
Published: August 2024

Background

An enterocutaneous fistula (ECF) is defined as an abnormal communication between the gastrointestinal tract and skin. ECFs are rarely encountered in clinical practice, yet are frequently difficult to treat. Few reports exist regarding the surgical techniques for the treatment of an ECF. Therefore, we report a case of refractory ECF with concomitant severe adhesions, in which we performed combined laparoscopic adhesiolysis and planned open conversion.

Case presentation

A 57-year-old female patient underwent a laparotomy for an ovarian cyst in her 20s. At 46 years, adhesiolysis without bowel resection was performed for adhesive small bowel obstruction (SBO). However, her symptoms did not improve. Eighteen days postoperatively, she underwent a reoperation and jejunostomy. An ECF developed post-reoperation; therefore, stoma closure and radical surgery for the ECF were planned. Due to the severe adhesions, only stoma closure was performed, based on intraoperative assessments. The patient was subsequently referred to our hospital. First, skin care around the fistula was provided during an outpatient visit. Appropriate sizing of the stoma pouch was performed, to improve erosions and ulcers. Thereafter, debridement of the perifistula skin and simple closure of the ECF outlet were attempted; however, the ECF recurred shortly thereafter. After 8 years of regular skin care, with the ECF remaining stable, however, manifesting as symptomatic SBO, she underwent laparoscopic adhesiolysis. This procedure was initiated in the epigastric region, where relatively fewer adhesions were anticipated. Post-open conversion, partial resection of the small intestine at four locations, including the fistula site, was performed. Postoperatively, jejunal edema and peristaltic dysfunction, due to narrowing of the superior mesenteric artery occurred. Regular drainage by percutaneous endoscopic gastrostomy was required. However, she improved and was discharged 3 months post-operatively. Three years post-operatively, the ECF and SBO did not recur.

Conclusions

We reported a case of refractory ECF in which we were able to safely perform surgery, by combining laparoscopic adhesiolysis and a planned open conversion. Therefore, the surgical approach used in this case may be an option for securing a safe surgical field, while avoiding collateral damage.
Automated cardiovascular MR myocardial scar quantification with unsupervised domain adaptation
Authors: Crawley Richard , Amirrajab Sina , Lustermans Didier , Holtackers Robert J. , Plein Sven , Veta Mitko , Breeuwer Marcel , Chiribiri Amedeo , Scannell Cian M.
Published: August 2024

Quantification of myocardial scar from late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) images can be facilitated by automated artificial intelligence (AI)-based analysis. However, AI models are susceptible to domain shifts in which the model performance is degraded when applied to data with different characteristics than the original training data. In this study, CycleGAN models were trained to translate local hospital data to the appearance of a public LGE CMR dataset. After domain adaptation, an AI scar quantification pipeline including myocardium segmentation, scar segmentation, and computation of scar burden, previously developed on the public dataset, was evaluated on an external test set including 44 patients clinically assessed for ischemic scar. The mean ± standard deviation Dice similarity coefficients between the manual and AI-predicted segmentations in all patients were similar to those previously reported: 0.76 ± 0.05 for myocardium and 0.75 ± 0.32 for scar, 0.41 ± 0.12 for scar in scans with pathological findings. Bland-Altman analysis showed a mean bias in scar burden percentage of -0.62% with limits of agreement from -8.4% to 7.17%. These results show the feasibility of deploying AI models, trained with public data, for LGE CMR quantification on local clinical data using unsupervised CycleGAN-based domain adaptation.

Relevance statement

Our study demonstrated the possibility of using AI models trained from public databases to be applied to patient data acquired at a specific institution with different acquisition settings, without additional manual labor to obtain further training labels.

Graphical Abstract
Scanning electron microscopy-based quantification of keratin and hyaluronic acid microstructure in electrospun scaffolds
Authors: Amajuoyi Joyce N. , Ilomuanya Margaret O. , Oseni Bukola , Azubuike Chukwuemeka P. , Krestou Athina , Vorp David A. , Tsamis Alkiviadis , Adeosun Samson O.
Published: August 2024

Background

The extracellular matrix (ECM) structural deficiencies in chronic wounds prevent the wounds from healing through natural physiological processes. Electrospun biocompatible polymers offer a platform to produce microstructure wound dressing materials that mimic the ECM containing various bioactives to address the deficiencies in the chronic wound healing process. Quantitative characterization of the electrospun fiber microstructure could provide valuable information on using fiber constructs to facilitate wound healing. This work employed a validated image analysis tool to quantitatively explain various parameters for the microstructure of six electrospun fiber constructs, D1{Polycaprolactone (PCL), Polyvinyl alcohol (PVA), Keratin}, D2{PCL, PVA, keratin, Co-enzyme Q10 (CoQ10)}, D3 (PCL, PVA, keratin, mupirocin), D4 (PCL, PVA, keratin, CoQ10, mupirocin, valsartan), D5 {PVA, Hyaluronic acid (HA)}, and D6 (PVA), using scanning electron microscopy imaging modality.

Results

The fiber intersection density (FID) parameter was quantified in the formulations, e.g., 0.272% for D5 and 0.416% for D4. Orientation histograms for D1 and D6 are characteristic of isotropic materials, while orientations for D2 and D3 indicate anisotropy with 2 preferred orientations in each formulation. D4 and D5 present orientations characteristic of transversely isotropic materials. The tortuosity for D2 and D4 indicates almost straight fiber segments, in contrast with undulated fiber segments in all other formulations. Furthermore, the mean fiber diameter was quantified, e.g., 1.414 and 1.630 mm for D3 and D4, respectively.

Conclusion

Co-electrospun PVA/PCL microfibers offer great potential for controlled delivery of bioactives needed to accelerate the healing of chronic wounds. This image-based analysis technology quantitatively characterized different formulations of electrospun fiber scaffolds. This analysis sets the stage for future study that utilizes microstructural information in finite element biomechanical modeling, to investigate possible influence of structure-based mechanical factors on the ECM restorative potential of wound dressings. Adjustment of electrospinning conditions could produce fabricated constructs like the native ECM structural components with a functional role in wound healing.
Women in otorhinolaryngology; their challenges and perspective: a cross-sectional study
Authors: Salem Eman H. , Khafagy Ahmed Y. , Fadel Michael , Moneir Waleed , El-Tawwab Mohamed Mostafa Abd , Abou-Elsaad Tamer , Khafagy Yasser W.
Published: August 2024

Background

The present study investigates the representation of women in the Otolaryngology department in a tertiary academic hospital, and the challenges they face during their residencies.

Methods

A questionnaire which included demographic information and a series of 54-questions of academic, clinical, social, psychological, and private practice challenges was electronically distributed among female residents registered in the Department of Otolaryngology in the last 10 years (2013–2022) throughout November 2023 to January 2024.

Results

Eighty-one female residents out of 103 registered (78.6%) responded to the distributed questionnaire highlighting the challenges they faced during their training period.

Conclusion

The current study addresses the barriers confronted by female residents in the department as well as identifying potential solutions that might help future encouragement of women to select otolaryngology as their specialty.
Reversible Gynecomastia and Hypogonadism Due to Usage of Commercial Performance-Enhancing Supplement Use
Authors: Chong Serena , Woolnough Catherine A , Koyyalamudi Sundar R , Perera Nimalie J
Published: August 2024

Commercially available performance-enhancing supplements can contain banned performance-enhancing drugs (PEDs) and undisclosed steroid hormones that can induce hormonal abnormalities with associated clinical signs. We present a case of a 40-year-old male who developed bilateral gynecomastia and biochemical hypogonadotropic hypogonadism with a corresponding 6-month history of consuming commercially available performance-enhancing supplements for gym workouts. These performance-enhancing supplements were found to contain amounts of RAD-140, a selective androgen receptor modulator, MK-677, a GH secretagogue and cardarine, all of which are banned PEDs. In vitro analysis also detected undisclosed hormones testosterone, estradiol, and GH in all 3 supplements, with further steroid analysis using liquid chromatography mass spectrometry identifying an unidentified compound coeluting close to the testosterone peak. Cessation of these supplements led to full resolution of symptoms including normalization of hypogonadotropic hypogonadism. This case highlights the need for clinicians to consider commercially available performance-enhancing supplements as potential sources of PEDs and exogenous steroid hormones that can have adverse clinical consequences.