bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the oral microbiome in obesity and metabolic disease: potential systemic implications and effects on taste perception
Authors: Schamarek Imke , Anders Lars , Chakaroun Rima M. , Kovacs Peter , Rohde-Zimmermann Kerstin
Published: May 2023

Obesity and its metabolic sequelae still comprise a challenge when it comes to understanding mechanisms, which drive these pandemic diseases. The human microbiome as a potential key player has attracted the attention of broader research for the past decade. Most of it focused on the gut microbiome while the oral microbiome has received less attention. As the second largest niche, the oral microbiome is associated with a multitude of mechanisms, which are potentially involved in the complex etiology of obesity and associated metabolic diseases. These mechanisms include local effects of oral bacteria on taste perception and subsequent food preference as well as systemic effects on adipose tissue function, the gut microbiome and systemic inflammation. This review summarizes a growing body of research, pointing towards a more prominent role of the oral microbiome in obesity and associated metabolic diseases than expected. Ultimately, our knowledge on the oral microbiome may support the development of new patient oriented therapeutic approaches inevitable to relieve the health burden of metabolic diseases and to reach long-term benefits in patients´ lives.
A YOLO-based AI system for classifying calcifications on spot magnification mammograms
Authors: Chen Jian-Ling , Cheng Lan-Hsin , Wang Jane , Hsu Tun-Wei , Chen Chin-Yu , Tseng Ling-Ming , Guo Shu-Mei
Published: May 2023

Objectives

Use of an AI system based on deep learning to investigate whether the system can aid in distinguishing malignant from benign calcifications on spot magnification mammograms, thus potentially reducing unnecessary biopsies.

Methods

In this retrospective study, we included public and in-house datasets with annotations for the calcifications on both craniocaudal and mediolateral oblique vies, or both craniocaudal and mediolateral views of each case of mammograms. All the lesions had pathological results for correlation. Our system comprised an algorithm based on You Only Look Once (YOLO) named adaptive multiscale decision fusion module. The algorithm was pre-trained on a public dataset, Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM), then re-trained and tested on the in-house dataset of spot magnification mammograms. The performance of the system was investigated by receiver operating characteristic (ROC) analysis.

Results

We included 1872 images from 753 calcification cases (414 benign and 339 malignant) from CBIS-DDSM. From the in-house dataset, 636 cases (432 benign and 204 malignant) with 1269 spot magnification mammograms were included, with all lesions being recommended for biopsy by radiologists. The area under the ROC curve for our system on the in-house testing dataset was 0.888 (95% CI 0.868–0.908), with a sensitivity of 88.4% (95% CI 86.9–8.99%), specificity of 80.8% (95% CI 77.6–84%), and an accuracy of 84.6% (95% CI 81.8–87.4%) at the optimal cutoff value. Using the system with two views of spot magnification mammograms, 80.8% benign biopsies could be avoided.

Conclusion

The AI system showed good accuracy for classification of calcifications on spot magnification mammograms which were all categorized as suspicious by radiologists, thereby potentially reducing unnecessary biopsies.
Biometals in Alzheimer disease: emerging therapeutic and diagnostic potential of molybdenum and iodine
Authors: Botchway Benson O. A. , Liu Xuehong , Zhou Yu , Fang Marong
Published: May 2023

The current ageing trend of the world population has, in part, accounted for Alzheimer disease (AD) being a public health issue in recent times. Although some progress has been made in clarifying AD-related pathophysiological mechanisms, effective intervention is still elusive. Biometals are indispensable to normal physiological functions of the human body—for example, neurogenesis and metabolism. However, their association with AD remains highly controversial. Copper (Cu) and zinc (Zn) are biometals that have been investigated at great length in relation to neurodegeneration, whereas less attention has been afforded to other trace biometals, such as molybdenum (Mo), and iodine. Given the above context, we reviewed the limited number of studies that have evidenced various effects following the usage of these two biometals in different investigative models of AD. Revisiting these biometals via thorough investigations, along with their biological mechanisms may present a solid foundation for not only the development of effective interventions, but also as diagnostic agents for AD.
The neuroprotective N-terminal amyloid-β core hexapeptide reverses reactive gliosis and gliotoxicity in Alzheimer’s disease pathology models
Authors: Lantz Megan J. , Roberts Alyssa M. , Delgado Donovan D. , Nichols Robert A.
Published: May 2023

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by accumulation of extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles, leading to chronic activation of astrocytes and microglia and persistent neuroinflammation. Aβ-linked activation of microglia and astrocytes leads to increased intracellular calcium and production of proinflammatory cytokines, impacting the progression of neurodegeneration. An N-terminal Aβ fragment (Aβ1–15) and a shorter hexapeptide core sequence within the N-Aβ fragment (N-Aβcore: Aβ10–15) have previously been shown to protect against Aβ-induced mitochondrial dysfunction, oxidative stress and apoptosis in neurons and rescue synaptic and spatial memory deficits in an APP/PSEN1 mouse model. Here, we hypothesized that the N-Aβ fragment and N-Aβcore are protective against Aβ-induced gliotoxicity, promoting a neuroprotective environment and potentially alleviating the characteristically persistent neuroinflammation present in AD.

Methods

We treated ex vivo organotypic brain slice cultures from an aged familial AD mouse model, 5xFAD, with the N-Aβcore and used immunocytochemistry to assess the impact on astrogliosis and microgliosis and alterations in synaptophysin-positive puncta engulfed by microglia. Isolated neuron/glia cultures, mixed glial cultures or a microglial cell line were treated with oligomeric human Aβ at concentrations mimicking the pathogenic concentrations (μM) observed in AD in the absence or presence of the non-toxic N-terminal Aβ fragments. Resultant changes in synaptic density, gliosis, oxidative stress, mitochondrial dysfunction, apoptosis, and the expression and release of proinflammatory markers were then determined.

Results

We demonstrate that the N-terminal Aβ fragments mitigated the phenotypic switch leading to astrogliosis and microgliosis induced by pathological concentrations of Aβ in mixed glial cultures and organotypic brain slice cultures from the transgenic 5xFAD mouse model, while protecting against Aβ-induced oxidative stress, mitochondrial dysfunction and apoptosis in isolated astrocytes and microglia. Moreover, the addition of the N-Aβcore attenuated the expression and release of proinflammatory mediators in microglial cells activated by Aβ and rescued microglia-mediated loss of synaptic elements induced by pathological levels of Aβ.

Conclusions

Together, these findings indicate the protective functions of the N-terminal Aβ fragments extend to reactive gliosis and gliotoxicity induced by Aβ, by preventing or reversing glial reactive states indicative of neuroinflammation and synaptic loss central to AD pathogenesis.
Accuracy of diagnostic tests in cardiac injury after blunt chest trauma: a systematic review and meta-analysis
Authors: Kyriazidis Ioannis Panagiotis , Jakob Dominik A. , Vargas Juliana Alexandra Hernández , Franco Oscar H. , Degiannis Elias , Dorn Patrick , Pouwels Sjaak , Patel Bijendra , Johnson Ian , Houdlen Christopher John , Whiteley Graham S. , Head Marion , Lala Anil , Mumtaz Haroon , Soler J. Agustin , Mellor Katie , Rawaf David , Ahmed Ahmed R. , Ahmad Suhaib J. S. , Exadaktylos Aristomenis
Published: May 2023

Introduction

The diagnosis of cardiac contusion, caused by blunt chest trauma, remains a challenge due to the non-specific symptoms it causes and the lack of ideal tests to diagnose myocardial damage. A cardiac contusion can be life-threatening if not diagnosed and treated promptly. Several diagnostic tests have been used to evaluate the risk of cardiac complications, but the challenge of identifying patients with contusions nevertheless remains.

Aim of the study

To evaluate the accuracy of diagnostic tests for detecting blunt cardiac injury (BCI) and its complications, in patients with severe chest injuries, who are assessed in an emergency department or by any front-line emergency physician.

Methods

A targeted search strategy was performed using Ovid MEDLINE and Embase databases from 1993 up to October 2022. Data on at least one of the following diagnostic tests: electrocardiogram (ECG), serum creatinine phosphokinase-MB level (CPK-MB), echocardiography (Echo), Cardiac troponin I (cTnI) or Cardiac troponin T (cTnT). Diagnostic tests for cardiac contusion were evaluated for their accuracy in meta-analysis. Heterogeneity was assessed using the I2 and the QUADAS-2 tool was used to assess bias of the studies.

Results

This systematic review yielded 51 studies (n = 5,359). The weighted mean incidence of myocardial injuries after sustaining a blunt force trauma stood at 18.3% of cases. Overall weighted mean mortality among patients with blunt cardiac injury was 7.6% (1.4–36.4%). Initial ECG, cTnI, cTnT and transthoracic echocardiography TTE all showed high specificity (> 80%), but lower sensitivity (< 70%). TEE had a specificity of 72.1% (range 35.8–98.2%) and sensitivity of 86.7% (range 40–99.2%) in diagnosing cardiac contusion. CK-MB had the lowest diagnostic odds ratio of 3.598 (95% CI: 1.832–7.068). Normal ECG accompanied by normal cTnI showed a high sensitivity of 85% in ruling out cardiac injuries.

Conclusion

Emergency physicians face great challenges in diagnosing cardiac injuries in patients following blunt trauma. In the majority of cases, joint use of ECG and cTnI was a pragmatic and cost-effective approach to rule out cardiac injuries. In addition, TEE may be highly accurate in identifying cardiac injuries in suspected cases.
Qualitative and semi-quantitative ultrasound assessment in delta and Omicron Covid-19 patients: data from high volume reference center
Authors: Granata Vincenza , Fusco Roberta , Villanacci Alberta , Grassi Francesca , Grassi Roberta , Di Stefano Federica , Petrone Ada , Fusco Nicoletta , Ianniello Stefania
Published: May 2023

Objective: to evaluate the efficacy of US, both qualitatively and semi-quantitatively, in the selection of treatment for the Covid-19 patient, using patient triage as the gold standard. Methods: Patients admitted to the Covid-19 clinic to be treated with monoclonal antibodies (mAb) or retroviral treatment and undergoing lung ultrasound (US) were selected from the radiological data set between December 2021 and May 2022 according to the following inclusion criteria: patients with proven Omicron variant and Delta Covid-19 infection; patients with known Covid-19 vaccination with at least two doses. Lung US (LUS) was performed by experienced radiologists. The presence, location, and distribution of abnormalities, such as B-lines, thickening or ruptures of the pleural line, consolidations, and air bronchograms, were evaluated. The anomalous findings in each scan were classified according to the LUS scoring system. Nonparametric statistical tests were performed. Results: The LUS score median value in the patients with Omicron variant was 1.5 (1–20) while the LUS score median value in the patients with Delta variant was 7 (3–24). A difference statistically significant was observed for LUS score values among the patients with Delta variant between the two US examinations (p value = 0.045 at Kruskal Wallis test). There was a difference in median LUS score values between hospitalized and non-hospitalized patients for both the Omicron and Delta groups (p value = 0.02 on the Kruskal Wallis test). For Delta patients groups the sensitivity, specificity, positive and negative predictive values, considering a value of 14 for LUS score for the hospitalization, were of 85.29%, 44.44%, 85.29% and 76.74% respectively. Conclusions: LUS is an interesting diagnostic tool in the context of Covid-19, it could allow to identify the typical pattern of diffuse interstitial pulmonary syndrome and could guide the correct management of patients.
Gastric cancer treatment: recent progress and future perspectives
Authors: Guan Wen-Long , He Ye , Xu Rui-Hua
Published: May 2023

Gastric cancer (GC) is one of the most common malignancies worldwide. Most patients are diagnosed at advanced stages due to the subtle symptoms of earlier disease and the low rate of regular screening. Systemic therapies for GC, including chemotherapy, targeted therapy and immunotherapy, have evolved significantly in the past few years. For resectable GC, perioperative chemotherapy has become the standard treatment. Ongoing investigations are exploring the potential benefits of targeted therapy or immunotherapy in the perioperative or adjuvant setting. For metastatic disease, there have been notable advancements in immunotherapy and biomarker-directed therapies recently. Classification based on molecular biomarkers, such as programmed cell death ligand 1 (PD-L1), microsatellite instability (MSI), and human epidermal growth factor receptor 2 (HER2), provides an opportunity to differentiate patients who may benefit from immunotherapy or targeted therapy. Molecular diagnostic techniques have facilitated the characterization of GC genetic profiles and the identification of new potential molecular targets. This review systematically summarizes the main research progress in systemic treatment for GC, discusses current individualized strategies and presents future perspectives.
N-acetyl-L-leucine for Niemann-Pick type C: a multinational double-blind randomized placebo-controlled crossover study
Authors: Fields T , M. Bremova T , Billington I , Churchill GC , Evans W , Fields C , Galione A , Kay R , Mathieson T , Martakis K , Patterson M , Platt F , Factor M , Strupp M
Published: May 2023

Background

Niemann-Pick disease type C (NPC) is a rare autosomal recessive neurodegenerative lysosomal disease characterized by multiple symptoms such as progressive cerebellar ataxia and cognitive decline. The modified amino acid N-acetyl-leucine has been associated with positive symptomatic and neuroprotective, disease-modifying effects in various studies, including animal models of NPC, observational clinical case studies, and a multinational, rater-blinded phase IIb clinical trial. Here, we describe the development of a study protocol (Sponsor Code “IB1001-301”) for the chronic treatment of symptoms in adult and pediatric patients with NPC.

Methods

This multinational double-blind randomized placebo-controlled crossover phase III study will enroll patients with a genetically confirmed diagnosis of NPC patients aged 4 years and older across 16 trial sites. Patients are assessed during a baseline period and then randomized (1:1) to one of two treatment sequences: IB1001 followed by placebo or vice versa. Each sequence consists of a 12-week treatment period. The primary efficacy endpoint is based on the Scale for the Assessment and Rating of Ataxia, and secondary outcomes include cerebellar functional rating scales, clinical global impression, and quality of life assessments.

Discussion

Pre-clinical as well as observational and phase IIb clinical trials have previously demonstrated that IB1001 rapidly improved symptoms, functioning, and quality of life for pediatric and adult NPC patients and is safe and well tolerated. In this placebo-controlled cross-over trial, the risk/benefit profile of IB1001 for NPC will be evaluated. It will also give information about the applicability of IB1001 as a therapeutic paradigm for other rare and common neurological disorders.

Trial registrations

The trial (IB1001-301) has been registered at www.clinicaltrials.gov (NCT05163288) and www.clinicaltrialsregister.eu (EudraCT: 2021–005356-10). Registered on 20 December 2021.
The metabolome and bacterial composition of high-moisture Italian ryegrass silage inoculated with lactic acid bacteria during ensiling
Authors: Xia Guang-hao , Wu Chang-rong , Zhang Ming-zhu , Yang Feng , Chen Chao , Hao Jun
Published: May 2023

Background

With its high nutritional value and productivity, Italian ryegrass as a biomass feedstock constantly supplies rumen degradable nitrogen and digestible fiber to ruminants. However, biofuel production is easily reduced during ensiling due to the high-moisture content of Italian ryegrass, leading to economic losses. Lactic acid bacteria inoculants could improve lignocellulosic degradation and fermentation quality and decrease dry matter loss during the bioprocessing of silage. Therefore, this study analyzed the effects of Lactobacillus buchneri TSy1-3 (HE), Lactobacillus rhamnosus BDy3-10 (HO), and the combination of HE and HO (M) on fermentation quality, bacterial community and metabolome in high-moisture Italian ryegrass silage during ensiling.

Results

The results showed that the pH value was significantly lower in the HO groups than in the other treatments at the end of ensiling, and the dry matter and acetic acid contents were significantly higher in the HO group than in the other inoculated groups. All inoculants decreased the diversity of the bacterial community and significantly increased the relative abundance of Lactobacillus. Inoculation with HO significantly improved the concentrations of organic acids, dipeptides, ferulic acid, apigenin, and laricitrin. Compared with Lactobacillus buchneri TSy1-3 (HE), HO significantly upregulated the flavonoid compounds in the flavone and flavonol biosynthesis pathway.

Conclusions

Overall, these findings suggest that inoculation with HO was beneficial for the development of Italian ryegrass as a biomass feedstock, improving fermentation quality, accelerating changes in bacterial community composition and increasing biofunctional metabolites in high-moisture Italian ryegrass silage.
Development of a primary care screening algorithm for the early detection of patients at risk of primary antibody deficiency
Authors: Messelink Marianne A. , Berbers Roos M. , van Montfrans Joris M. , Ellerbroek Pauline M. , Gladiator André , Welsing Paco M. J. , Leavis Helen
Published: May 2023

Background

Primary antibody deficiencies (PAD) are characterized by a heterogeneous clinical presentation and low prevalence, contributing to a median diagnostic delay of 3–10 years. This increases the risk of morbidity and mortality from undiagnosed PAD, which may be prevented with adequate therapy. To reduce the diagnostic delay of PAD, we developed a screening algorithm using primary care electronic health record (EHR) data to identify patients at risk of PAD. This screening algorithm can be used as an aid to notify general practitioners when further laboratory evaluation of immunoglobulins should be considered, thereby facilitating a timely diagnosis of PAD.

Methods

Candidate components for the algorithm were based on a broad range of presenting signs and symptoms of PAD that are available in primary care EHRs. The decision on inclusion and weight of the components in the algorithm was based on the prevalence of these components among PAD patients and control groups, as well as clinical rationale.

Results

We analyzed the primary care EHRs of 30 PAD patients, 26 primary care immunodeficiency patients and 58,223 control patients. The median diagnostic delay of PAD patients was 9.5 years. Several candidate components showed a clear difference in prevalence between PAD patients and controls, most notably the mean number of antibiotic prescriptions in the 4 years prior to diagnosis (5.14 vs. 0.48). The final algorithm included antibiotic prescriptions, diagnostic codes for respiratory tract and other infections, gastro-intestinal complaints, auto-immune symptoms, malignancies and lymphoproliferative symptoms, as well as laboratory values and visits to the general practitioner.

Conclusions

In this study, we developed a screening algorithm based on a broad range of presenting signs and symptoms of PAD, which is suitable to implement in primary care. It has the potential to considerably reduce diagnostic delay in PAD, and will be validated in a prospective study.

Trial registration The consecutive prospective study is registered at clinicaltrials.gov under NCT05310604
Ruptured bilateral brain arteriovenous malformations in a young woman with early pregnancy: a case report
Authors: Magitta Ng’weina F. , Sindato Emmanuel M. , Meda John R. , Toroha Hasna N. , Meremo Alfred J.
Published: May 2023

Background

Brain arteriovenous malformations (AVMs) are rare congenital developmental vascular lesions, and often presents with symptoms upon rupture. The controversy exists as to whether pregnancy confers an increased risk of intracranial hemorrhage. The diagnosis of brain AVMs, in the absence of brain imaging, is challenging in resource-limited settings, particularly in sub-Saharan Africa.

Case presentation

A 22-year old black African woman, primigravida at 14 weeks of gestation, presented with a history of persistent throbbing headache which was treated at primary health care facilities with analgesics and anti-migraine medications without relief. She later developed severe headache 2 weeks prior to admission and one-day history of serial partial generalized tonic–clonic seizures which were followed by post-ictal confusion and persistent right upper limb weakness. Initial evaluation revealed her to be pregnant and she later underwent a brain magnetic resonance angiography (MRA) at a university teaching hospital which revealed bleeding bilateral parietal AMVs with intracerebral haematoma and associated perilesional vasogenic oedema. The patient was managed conservatively using antifibrinolytic drugs and prophylactic anti-seizure drugs. Seven months later, she underwent a control brain MRA which revealed resolution of intracranial haematoma and associated vasogenic oedema and had her seizures well controlled. The headache had subsided and the pregnancy was allowed to continue to term under close obstetric and neurological observation. On follow up visits she reported episodes of nasal bleeding which upon ENT examination revealed nasal AVMs, suggesting the diagnosis of hereditary hemorrhagic telangiectasia (HHT).

Conclusion

AVMs are rare but should prompt suspicion in young patients with atypical Central Nervous System (CNS) manifestations without evident underlying causes.
Deletion of Rap-phosphatases for quorum sensing control in Bacillus and its effect on surfactin production
Authors: Treinen Chantal , Biermann Lennart , Vahidinasab Maliheh , Heravi Kambiz Morabbi , Lilge Lars , Hausmann Rudolf , Henkel Marius
Published: May 2023

The complex regulatory network in Bacillus, known as quorum sensing, offers many opportunities to modify bacterial gene expression and hence to control bioprocesses. One target regulated by this mechanism is the activity of the PsrfA promoter, which is engaged in the formation of lipopeptide surfactin. It was hypothesised that deletion of rapC, rapF and rapH, encoding for prominent Rap-phosphatases known to affect PsrfA activity, would enhance surfactin production. Therefore, these genes were deleted in a sfp+ derivative of B. subtilis 168 with subsequent evaluation of quantitative data. Up to the maximum product formation of the reference strain B. subtilis KM1016 after 16 h of cultivation, the titers of the rap deletion mutants did not exceed the reference. However, an increase in both product yield per biomass YP/X and specific surfactin productivity qsurfactin was observed, without any considerable effect on the ComX activity. By extending the cultivation time, a 2.7-fold increase in surfactin titer was observed after 24 h for strain CT10 (ΔrapC) and a 2.5-fold increase for CT11 (ΔrapF) compared to the reference strain KM1016. In addition, YP/X was again increased for strains CT10 and CT11, with values of 1.33 g/g and 1.13 g/g, respectively. Interestingly, the effect on surfactin titer in strain CT12 (ΔrapH) was not as distinct, although it achieved the highest promoter activity (PsrfA-lacZ). The data presented support the possibility of involving the quorum sensing system of Bacillus in bioprocess control as shown here on the example of lipopeptide production.
A systematic review and meta-analysis of long COVID symptoms
Authors: Natarajan Arun , Shetty Ashish , Delanerolle Gayathri , Zeng Yutian , Zhang Yingzhe , Raymont Vanessa , Rathod Shanaya , Halabi Sam , Elliot Kathryn , Shi Jian Qing , Phiri Peter
Published: May 2023

Background

Ongoing symptoms or the development of new symptoms following a SARS-CoV-2 diagnosis has caused a complex clinical problem known as “long COVID” (LC). This has introduced further pressure on global healthcare systems as there appears to be a need for ongoing clinical management of these patients. LC personifies heterogeneous symptoms at varying frequencies. The most complex symptoms appear to be driven by the neurology and neuropsychiatry spheres.

Methods

A systematic protocol was developed, peer reviewed, and published in PROSPERO. The systematic review included publications from the 1st of December 2019–30th June 2021 published in English. Multiple electronic databases were used. The dataset has been analyzed using a random-effects model and a subgroup analysis based on geographical location. Prevalence and 95% confidence intervals (CIs) were established based on the data identified.

Results

Of the 302 studies, 49 met the inclusion criteria, although 36 studies were included in the meta-analysis. The 36 studies had a collective sample size of 11,598 LC patients. 18 of the 36 studies were designed as cohorts and the remainder were cross-sectional. Symptoms of mental health, gastrointestinal, cardiopulmonary, neurological, and pain were reported.

Conclusions

The quality that differentiates this meta-analysis is that they are cohort and cross-sectional studies with follow-up. It is evident that there is limited knowledge available of LC and current clinical management strategies may be suboptimal as a result. Clinical practice improvements will require more comprehensive clinical research, enabling effective evidence-based approaches to better support patients.
A randomized controlled trial for a peer-facilitated telemedicine hepatitis c treatment intervention for people who use drugs in rural communities: study protocol for the “peer tele-HCV” study
Authors: Herink Megan C. , Seaman Andrew , Leichtling Gillian , Larsen Jessica E. , Gailey Tonhi , Cook Ryan , Thomas Ann , Korthuis P. Todd
Published: May 2023

Background

Hepatitis C virus (HCV) transmission is primarily driven by injection drug use, and acute HCV infection rates are increased in rural communities with substantial barriers to care. Treatment of HCV in persons who use drugs (PWUD) is cost effective, decreases high risk behaviors and HCV transmission, and achieves high rates of treatment completion and sustained viral response. Adapting HCV care delivery to utilize peer support specialists, telemedicine technology, and streamlined testing and treatment strategies can better reach rural populations living with HCV.

Methods

This is an open label, two-arm, non-blinded, randomized controlled trial designed to test the superiority of peer-facilitated and streamlined telemedicine HCV care (peer tele-HCV) compared to enhanced usual care (EUC) among PWUD in rural Oregon. In the intervention arm, peers conduct HCV screening in the community, facilitate pretreatment evaluation and linkage to telemedicine hepatitis C treatment providers, and support participants in HCV medication adherence. For participants assigned to EUC, peers facilitate pretreatment evaluation and referral to community-based treatment providers. The primary outcome is sustained virologic response at 12 weeks post treatment (SVR12). Secondary outcomes include: (1) HCV treatment initiation, (2) HCV treatment completion, (3) engagement with harm reduction resources, (4) rates of substance use, and (5) engagement in addiction treatment resources. The primary and secondary outcomes are analyzed using intention-to-treat (ITT) comparisons between telemedicine and EUC. A qualitative analysis will assess patient, peer, and clinician experiences of peer-facilitated telemedicine hepatitis C treatment.

Discussion

This study uses a novel peer-based telemedicine delivery model with streamlined testing protocols to improve access to HCV treatment in rural communities with high rates of injection drug use and ongoing disease transmission. We hypothesize that the peer tele-HCV model will increase treatment initiation, treatment completion, SVR12 rates, and engagement with harm reduction services compared to EUC.

Trial registration This trial has been registered with ClinicalTrials.gov (clinicaltrials.gov NCT04798521)
Music therapy, neural processing, and craving reduction: an RCT protocol for a mixed methods feasibility study in a Community Substance Misuse Treatment Service
Authors: Fachner Jörg , Maidhof Clemens , Murtagh Daniel , De Silva Devon , Pasqualitto Filippo , Fernie Paul , Panin Francesca , Michell Andrew , Muller-Rodriguez Leonardo , Odell-Miller Helen
Published: May 2023

Background

Music therapy has been shown to be effective for multiple clinical endpoints associated with substance use disorder such as craving reduction, emotion regulation, depression, and anxiety, but there are a lack of studies investigating those effects in UK Community Substance Misuse Treatment Services (CSMTSs). Furthermore, there is a demand for identifying music therapy mechanisms of change and related brain processes for substance use disorder treatment. The present study aims to evaluate the feasibility and acceptability of music therapy and a pre-test, post-test, and in-session measurement battery in a CSMTS.

Methods

Fifteen participants, from a community service based in London, will take part in a mixed-methods non-blind randomized-controlled trial. Ten participants will receive six-weekly sessions of music therapy in addition to the standard treatment offered by the CSMTS—five of them will receive individual music therapy and five of them will receive group music therapy—while a further five participants will act as a control group receiving standard treatment only.

Satisfaction and acceptability will be evaluated in focus groups with service users and staff members following the final treatment session. Moreover, attendance and completion rates will be monitored throughout the intervention. Subjective and behavioral indexes will be assessed before and after the interventions to explore the effects of music therapy on craving, substance use, symptoms of depression and anxiety, inhibitory control, and will be correlated with associated neurophysiological signatures. In-session analysis of two individual music therapy sessions will serve to explore how music and emotion are processed in the brain within the therapy. The data collected at each step will be included in an intention-to-treat analysis basis.

Discussion

This study will provide a first report on the feasibility of music therapy as an intervention for participants with substance use disorder engaged within a community service. It will also provide valuable information regarding the implementation of a multifaceted methodology that includes neurophysiological, questionnaire-based, and behavioral assessments in this cohort. Notwithstanding the limitation of a small sample size, the present study will provide novel preliminary data regarding neurophysiological outcomes in participants with substance use disorder that received music therapy.

Trial Registration: ClinicalTrails.gov, NCT0518061, Registered 6 January 2022, https://clinicaltrials.gov/ct2/show/NCT05180617
Correlation between dental arch form and OSA severity in adult patients: an observational study
Authors: Ciavarella Domenico , Campobasso Alessandra , Conte Elisa , Burlon Giuseppe , Guida Laura , Montaruli Graziano , Cassano Michele , Laurenziello Michele , Illuzzi Gaetano , Tepedino Michele
Published: May 2023

Background

The role of interdental widths and palatal morphology on the development of obstructive sleep apnea (OSA) has not been well investigated in adult patients yet. The aim of this paper was to assess the morphology of maxilla and mandibular dental arches on three-dimensional (3D) casts and to correlate these measurements with the severity of OSA.

Methods

Sixty-four patients (8 women and 56 men, mean age 52.4) with a diagnosis of mild-to-moderate OSA were retrospectively enrolled. On each patient, home sleep apnea test and 3D dental models were collected. Apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were recorded, as well as the dental measurements including inter-molar distance, anterior and posterior widths of maxillary and mandibular arches, upper and lower arch lengths, palatal height, and palatal surface area. The respiratory and dental variables were then correlated.

Result

A statistically inverse correlation was found between ODI and anterior width of lower arch, maxillary arch length, palatal height, and palatal area. AHI showed a significant inverse correlation with anterior width of mandibular arch and maxillary length.

Conclusion

A significant inverse correlation between maxillary and mandibular morphology and respiratory parameters was shown in the present paper.
Trends in adults’ energy imbalance gaps over two decades in Belgium using system dynamics modelling
Authors: Fallah-Fini Saeideh , Rezaei Tannaz , De Ridder Karin , Vandevijvere Stefanie
Published: May 2023

Background

The energy imbalance gap (EIG) represents the average daily difference between energy intake and energy expenditure. The maintenance energy gap (MEG) captures the increased energy intake needed to maintain a higher average bodyweight compared with an initial distribution of bodyweight. This study quantified the dynamics of the EIG and MEG over time and across different genders/regions/BMI groups for Belgian adults.

Methods

A validated system dynamics model was adapted to estimate the trends/dynamics of the EIG among different subpopulations over two decades in Belgium. The model was calibrated using data from the six Belgian national Health Interview Surveys (1997, 2001, 2004, 2008, 2013, 2018).

Results

EIG was negative for all BMI groups among Belgian females in 2018, implying the start of a decrease in prevalence of overweight/obesity in this subpopulation. However, this was not the case among Belgian males. Flemish and Walloon males had positive EIGs across BMI groups in 2018, however, Brussels’ males showed negative EIGs across BMI groups. Flemish and Brussels’ females showed negative EIGs across all BMI groups in 2018, while Walloon females showed positive EIGs across almost all BMI groups. According to the MEG, Belgian men consumed (and expended) on average 59 kcal/day more in 2018 than in 1997 to maintain their heavier body weight. The MEG for Belgian women was 46 kcal/day in 2018, triple the MEG in 2004.

Conclusions

The detailed heterogeneous trends of the EIG describe the obesity patterns for different subpopulations in Belgium and could be used to model the differential effects of specific nutrition policies targeting energy intake.
Scleral appearance is not a correlate of domestication in mammals
Authors: Caspar Kai R. , Hüttner Lisa , Begall Sabine
Published: May 2023

Numerous hypotheses try to explain the unusual appearance of the human eye with its bright sclera and transparent conjunctiva and how it could have evolved from a dark-eyed phenotype, as is present in many non-human primates. Recently, it has been argued that pigmentation defects induced by self-domestication may have led to bright-eyed ocular phenotypes in humans and some other primate lineages, such as marmosets. However, it has never been systematically studied whether actual domesticated mammals consistently deviate from wild mammals in regard to their conjunctival pigmentation and if this trait might therefore be part of a domestication syndrome. Here, we test this idea by drawing phylogenetically informed comparisons from a photographic dataset spanning 13 domesticated mammal species and their closest living wild relatives (n ≥ 15 photos per taxon). We did not recover significant differences in scleral appearance or irido-scleral contrast between domesticated and wild forms, suggesting that conjunctival depigmentation, unlike cutaneous pigmentation disorders, is not a general correlate of domestication. Regardless of their domestication status, macroscopically depigmented conjunctivae were observed in carnivorans and lagomorphs, whereas ungulates generally displayed darker eyes. For some taxa, we observed pronounced intraspecific variation, which should be addressed in more exhaustive future studies. Based on our dataset, we also present preliminary evidence for a general increase of conjunctival pigmentation with eye size in mammals. Our findings suggest that conjunctival depigmentation in humans is not a byproduct of self-domestication, even if we assume that our species has undergone such a process in its recent evolutionary history.
Comparative framework for AC-microgrid protection schemes: challenges, solutions, real applications, and future trends
Authors: Sheta Ahmed N. , Abdulsalam Gabr M. , Sedhom Bishoy E. , Eladl Abdelfattah A.
Published: May 2023

With the rapid development of electrical power systems in recent years, microgrids (MGs) have become increasingly prevalent. MGs improve network efficiency and reduce operating costs and emissions because of the integration of distributed renewable energy sources (RESs), energy storage, and source-load management systems. Despite these advances, the decentralized architecture of MGs impacts the functioning patterns of the entire system, including control strategy, energy management philosophy, and protection scheme. In this context, developing a convenient protection strategy for MGs is challenging because of various obstacles, such as the significant variance in short-circuit values under different operating modes, two-way power flow, asynchronous reclosing, protection blinding, sympathetic tripping, and loss of coordination. In light of these challenges, this paper reviews prior research on proposed protection schemes for AC-MGs to thoroughly evaluate network protection's potential issues. The paper also provides a comprehensive overview of the MG structure and the associated protection challenges, solutions, real applications, and future trends.
Association between thoracic and third lumbar CT-derived muscle mass and density in Caucasian patients without chronic disease: a proof-of-concept study
Authors: Brath Mia Solholt Godthaab , Sahakyan Marina , Mark Esben Bolvig , Frøkjær Jens Brøndum , Rasmussen Henrik Højgaard , Østergaard Lasse Riis , Weinreich Ulla Møller
Published: May 2023

Background

Computed tomography (CT) is increasingly used in the clinical workup, and existing scan contains unused body composition data, potentially useful in a clinical setting. However, there is no healthy reference for contrast-enhanced thoracic CT-derived muscle measures. Therefore, we aimed at investigating whether there is a correlation between each of the thoracic and third lumbar vertebra level (L3) skeletal muscle area (SMA), skeletal muscle index (SMI), and skeletal muscle density (SMD) at contrast-enhanced CT in patients without chronic disease.

Methods

A proof-of-concept retrospective observational study was based on Caucasian patients without chronic disease, who received CT for trauma between 2012 and 2014. Muscle measures were assessed using a semiautomated threshold-based software by two raters independently. Pearson’s correlation between each thoracic level and third lumbar and intraclass correlation between two raters and test–retest with SMA as proxy parameters were used.

Results

Twenty-one patients (11 males, 10 females; median age 29 years) were included. The second thoracic vertebra (T2) had the highest median of cumulated SMA (males 314.7 cm2, females 118.5 cm2) and SMI (97.8 cm2/m2 and 70.4 cm2/m2, respectively). The strongest SMA correlation was observed between T5 and L3 (r = 0.970), the SMI between T11 and L3 (r = 0.938), and the SMD between the T10 and L3 (r = 0.890).

Conclusions

This study suggests that any of the thoracic levels can be valid to assess skeletal muscle mass. However, the T5 may be most favourable for measuring SMA, the T11 for SMI, and T10 for SMD when using contrast-enhanced thoracic CT.

Relevance statement

In COPD patients, a CT-derived thoracic muscle mass assessment may help identify who would benefit from focused pulmonary rehabilitation: thoracic contrast-enhanced CT conducted as part of the standard clinical workup can be used for this evaluation.

Key points

• Any thoracic level can be used to assess thoracic muscle mass.

• Thoracic level 5 is strongly associated with the 3rd lumbar muscle area.

• A strong correlation between the thoracic level 11 and the 3rd lumbar muscle index.

• Thoracic level 10 is strongly associated with the 3rd lumbar muscle density.

Graphical Abstract
Glioma Metabolic Feedback In Situ: A First-In-Human Pharmacodynamic Trial of Difluoromethylornithine + AMXT-1501 Through High–Molecular Weight Microdialysis
Authors: Riviere-Cazaux Cecile , Neth Bryan J. , Hoplin Matthew D. , Wessel Bambi , Miska Jason , Kizilbash Sani H. , Burns Terry C.
Published: May 2023

BACKGROUND AND OBJECTIVES:

No new drug has improved survival for glioblastoma since temozolomide in 2005, due in part to the relative inaccessibility of each patientʼs individualized tumor biology and its response to therapy. We have identified a conserved extracellular metabolic signature of enhancing high-grade gliomas enriched for guanidinoacetate (GAA). GAA is coproduced with ornithine, the precursor to protumorigenic polyamines through ornithine decarboxylase (ODC). AMXT-1501 is a polyamine transporter inhibitor that can overcome tumoral resistance to the ODC inhibitor, difluoromethylornithine (DFMO). We will use DFMO with or without AMXT-1501 to identify candidate pharmacodynamic biomarkers of polyamine depletion in patients with high-grade gliomas in situ. We aim to determine (1) how blocking polyamine production affects intratumoral extracellular guanidinoacetate abundance and (2) the impact of polyamine depletion on the global extracellular metabolome within live human gliomas in situ.

METHODS:

DFMO, with or without AMXT-1501, will be administered postoperatively in 15 patients after clinically indicated subtotal resection for high-grade glioma. High–molecular weight microdialysis catheters implanted into residual tumor and adjacent brain will be used for postoperative monitoring of extracellular GAA and polyamines throughout therapeutic intervention from postoperative day (POD) 1 to POD5. Catheters will be removed on POD5 before discharge.

EXPECTED OUTCOMES:

We anticipate that GAA will be elevated in tumor relative to adjacent brain although it will decrease within 24 hours of ODC inhibition with DFMO. If AMXT-1501 effectively increases the cytotoxic impact of ODC inhibition, we expect an increase in biomarkers of cytotoxicity including glutamate with DFMO + AMXT-1501 treatment when compared with DFMO alone.

DISCUSSION:

Limited mechanistic feedback from individual patientsʼ gliomas hampers clinical translation of novel therapies. This pilot Phase 0 study will provide in situ feedback during DFMO + AMXT-1501 treatment to determine how high-grade gliomas respond to polyamine depletion.
Evaluation of postgraduate family medicine trainee’s knowledge and attitude following an online Educational Module in Palliative Care: A descriptive study
Authors: Jabeen Ismat , Usman Tayyabah , Asad Munazza , Qureshi Asra , Waqar Muhammad Atif
Published: May 2023

Objectives: To identify improvement in knowledge and attitude of Family Medicine (FM) postgraduate trainees (PGT) towards Palliative care (PC) in order to provide effective care to the patients with advanced disease.

Methods: A cross-sectional study was conducted over eight weeks from 1st July till 3rd September 2021 at Family Medicine Department, Aga Khan University Hospital (AKUH). PGT who willingly signed the written informed consent were enrolled in the study. Descriptive analysis, frequencies, proportions and thematic approach were used for data analysis. Data was analyzed using SPSS version 23.

Results: FM-PGT were included in the study. Improvement in knowledge was observed in posttest scores along with positive change in their attitude and improved perception of level of confidence for managing PC patients. Overall assessment of PCM was positive.

Conclusion: This PCM seems to be a useful tool for PC training in postgraduate medical education (PGME). This highlights some useful aspects for future applications in PC education and training.

doi: https://doi.org/10.12669/pjms.39.4.6984

How to cite this: Jabeen I, Usman T, Asad M, Qureshi A, Waqar MA. Evaluation of postgraduate family medicine trainee’s knowledge and attitude following an online Educational Module in Palliative Care: A descriptive study. Pak J Med Sci. 2023;39(4):---------.  doi: https://doi.org/10.12669/pjms.39.4.6984

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