bluuebunny/crossref_metadata_2025 huggingface dataset:
Conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs
Authors: Szabó Adrienn , Schlett Katalin , Szücs Attila
Published: September 2021

Activity-dependent regulation of intrinsic excitability has been shown to greatly contribute to the overall plasticity of neuronal circuits. Such neuroadaptations are commonly investigated in patch clamp experiments using current step stimulation and the resulting input-output functions are analyzed to quantify alterations in intrinsic excitability. However, it is rarely addressed, how such changes translate to the function of neurons when they operate under natural synaptic inputs. Still, it is reasonable to expect that a strong correlation and near proportional relationship exist between static firing responses and those evoked by synaptic drive. We challenge this view by performing a high-yield electrophysiological analysis of cultured mouse hippocampal neurons using both standard protocols and simulated synaptic inputs via dynamic clamp. We find that under these conditions the neurons exhibit vastly different firing responses with surprisingly weak correlation between static and dynamic firing intensities. These contrasting responses are regulated by two intrinsic K-currents mediated by Kv1 and Kir channels, respectively. Pharmacological manipulation of the K-currents produces differential regulation of the firing output of neurons. Static firing responses are greatly increased in stuttering type neurons under blocking their Kv1 channels, while the synaptic responses of the same neurons are less affected. Pharmacological blocking of Kir-channels in delayed firing type neurons, on the other hand, exhibit the opposite effects. Our subsequent computational model simulations confirm the findings in the electrophysiological experiments and also show that adaptive changes in the kinetic properties of such currents can even produce paradoxical regulation of the firing output.
ISOTOPE: ISOform-guided prediction of epiTOPEs in cancer
Authors: Trincado Juan L. , Reixachs-Solé Marina , Pérez-Granado Judith , Fugmann Tim , Sanz Ferran , Yokota Jun , Eyras Eduardo
Published: September 2021

Immunotherapies provide effective treatments for previously untreatable tumors and identifying tumor-specific epitopes can help elucidate the molecular determinants of therapy response. Here, we describe a pipeline, ISOTOPE (ISOform-guided prediction of epiTOPEs In Cancer), for the comprehensive identification of tumor-specific splicing-derived epitopes. Using RNA sequencing and mass spectrometry for MHC-I associated proteins, ISOTOPE identified neoepitopes from tumor-specific splicing events that are potentially presented by MHC-I complexes. Analysis of multiple samples indicates that splicing alterations may affect the production of self-epitopes and generate more candidate neoepitopes than somatic mutations. Although there was no difference in the number of splicing-derived neoepitopes between responders and non-responders to immune therapy, higher MHC-I binding affinity was associated with a positive response. Our analyses highlight the diversity of the immunogenic impacts of tumor-specific splicing alterations and the importance of studying splicing alterations to fully characterize tumors in the context of immunotherapies. ISOTOPE is available athttps://github.com/comprna/ISOTOPE.
Integration, coincidence detection and resonance in networks of spiking neurons expressing Gamma oscillations and asynchronous states
Authors: Susin Eduarda , Destexhe Alain
Published: September 2021

Gamma oscillations are widely seen in the awake and sleeping cerebral cortex, but the exact role of these oscillations is still debated. Here, we used biophysical models to examine how Gamma oscillations may participate to the processing of afferent stimuli. We constructed conductance-based network models of Gamma oscillations, based on different cell types found in cerebral cortex. The models were adjusted to extracellular unit recordings in humans, where Gamma oscillations always coexist with the asynchronous firing mode. We considered three different mechanisms to generate Gamma, first a mechanism based on the interaction between pyramidal neurons and interneurons (PING), second a mechanism in which Gamma is generated by interneuron networks (ING) and third, a mechanism which relies on Gamma oscillations generated by pacemaker chattering neurons (CHING). We find that all three mechanisms generate features consistent with human recordings, but that the ING mechanism is most consistent with the firing rate change inside Gamma bursts seen in the human data. We next evaluated the responsiveness and resonant properties of these networks, contrasting Gamma oscillations with the asynchronous mode. We find that for both slowly-varying stimuli and precisely-timed stimuli, the responsiveness is generally lower during Gamma compared to asynchronous states, while resonant properties are similar around the Gamma band. We could not find conditions where Gamma oscillations were more responsive. We therefore predict that asynchronous states provide the highest responsiveness to external stimuli, while Gamma oscillations tend to overall diminish responsiveness.
Early warning systems (EWSs) for chikungunya, dengue, malaria, yellow fever, and Zika outbreaks: What is the evidence? A scoping review
Authors: Hussain-Alkhateeb Laith , Rivera Ramírez Tatiana , Kroeger Axel , Gozzer Ernesto , Runge-Ranzinger Silvia
Published: September 2021

Background

Early warning systems (EWSs) are of increasing importance in the context of outbreak-prone diseases such as chikungunya, dengue, malaria, yellow fever, and Zika. A scoping review has been undertaken for all 5 diseases to summarize existing evidence of EWS tools in terms of their structural and statistical designs, feasibility of integration and implementation into national surveillance programs, and the users’ perspective of their applications.

Methods

Data were extracted from Cochrane Database of Systematic Reviews (CDSR), Google Scholar, Latin American and Caribbean Health Sciences Literature (LILACS), PubMed, Web of Science, and WHO Library Database (WHOLIS) databases until August 2019. Included were studies reporting on (a) experiences with existing EWS, including implemented tools; and (b) the development or implementation of EWS in a particular setting. No restrictions were applied regarding year of publication, language or geographical area.

Findings

Through the first screening, 11,710 documents for dengue, 2,757 for Zika, 2,706 for chikungunya, 24,611 for malaria, and 4,963 for yellow fever were identified. After applying the selection criteria, a total of 37 studies were included in this review. Key findings were the following: (1) a large number of studies showed the quality performance of their prediction models but except for dengue outbreaks, only few presented statistical prediction validity of EWS; (2) while entomological, epidemiological, and social media alarm indicators are potentially useful for outbreak warning, almost all studies focus primarily or exclusively on meteorological indicators, which tends to limit the prediction capacity; (3) no assessment of the integration of the EWS into a routine surveillance system could be found, and only few studies addressed the users’ perspective of the tool; (4) almost all EWS tools require highly skilled users with advanced statistics; and (5) spatial prediction remains a limitation with no tool currently able to map high transmission areas at small spatial level.

Conclusions

In view of the escalating infectious diseases as global threats, gaps and challenges are significantly present within the EWS applications. While some advanced EWS showed high prediction abilities, the scarcity of tool assessments in terms of integration into existing national surveillance systems as well as of the feasibility of transforming model outputs into local vector control or action plans tends to limit in most cases the support of countries in controlling disease outbreaks.
Platelet HMGB1 in Platelet-Rich Plasma (PRP) promotes tendon wound healing
Authors: Zhang Jianying , Li Feng , Augi Tyler , Williamson Kelly M. , Onishi Kentaro , Hogan MaCalus V. , Neal Matthew D. , Wang James H.-C.
Published: September 2021

Platelet-rich plasma (PRP) is a widely used autologous treatment for tendon injuries in clinics. Platelets (PLTs) are a major source of high mobility group box1 (HMGB1) that is gaining attention as a chemoattractant that can recruit stem cells to the wound area to enhance healing of injured tissues; however, the contribution of PLT HMGB1 in wounded tendon healing remains unexplored. This study investigated the effect of PLT HMGB1 within PRP on tendon healing using PLT HMGB1 knockout (KO) and GFP mice. A window defect was created in the patellar tendons of both groups of mice, and wounds were treated with either saline, PRP isolated from PLT HMGB1-KO mice, or PRP isolated from GFP mice. Seven days post-treatment, animals were sacrificed and analyzed by gross inspection, histology, and immunostaining for characteristic signs of tendon healing and repair. Our results showed that in comparison to mice treated with PRP from PLT HMGB1-KO mice, wounds treated with PRP from GFP mice healed faster and exhibited a better organization in tendon structure. Mice treated with PRP from PLT HMGB1-KO mice produced tendon tissue with large premature wound areas and low cell densities. However, wounds of PLT HMGB1-KO mice showed better healing with PRP from HMGB1-KO mice compared to saline treatment. Moreover, wounds treated with PRP from GFP mice had increased extracellular HMGB1, decreased CD68, increased stem cell markers CD146 and CD73, and increased collagen III protein expression levels compared to those treated with PRP from PLT HMGB1-KO mice. Thus, PLT HMGB1 within PRP plays an important role in tendon wound healing by decreasing inflammation, increasing local HMGB1 levels, and recruiting stem cells to the wound area in the tendon. Our findings also suggest that the efficacy of PRP treatment for tendon injuries in clinics may depend on PLT HMGB1 within PRP preparations.
SARS-CoV-2 infection: Initial viral load (iVL) predicts severity of illness/outcome, and declining trend of iVL in hospitalized patients corresponds with slowing of the pandemic
Authors: El Zein Said , Chehab Omar , Kanj Amjad , Akrawe Sandy , Alkassis Samer , Mishra Tushar , Shatta Maya , El-Hor Nivine , Salimnia Hossein , Chandrasekar Pranatharthi
Published: September 2021

Background

Hospitalization of patients infected with the severe acute respiratory syndrome virus 2 (SARS-CoV-2) have remained considerable worldwide. Patients often develop severe complications and have high mortality rates. The cycle threshold (Ct) value derived from nasopharyngeal swab samples using real time polymerase chain reaction (RT-PCR) may be a useful prognostic marker in hospitalized patients with SARS-CoV-2 infection, however, its role in predicting the course of the pandemic has not been evaluated thus far.

Methods

We conducted a retrospective cohort study which included all patients who had a nasopharyngeal sample positive for SARS-CoV-2 between April 4 –June 5, 2020. The Ct value was used to estimate the number of viral particles in a patient sample. The trend in initial viral load on admission on a population level was evaluated. Moreover, patient characteristics and outcomes stratified by viral load categories were compared and initial viral load was assessed as an independent predictor of intubation and in-hospital mortality.

Results

A total of 461 hospitalized patients met the inclusion criteria. This study consisted predominantly of acutely infected patients with a median of 4 days since symptom onset to PCR. As the severity of the pandemic eased, there was an increase in the percentage of samples in the low initial viral load category, coinciding with a decrease in deaths. Compared to an initial low viral load, a high initial viral load was an independent predictor of in-hospital mortality (OR 5.5, CI 3.1–9.7, p < 0.001) and intubation (OR 1.82 CI 1.07–3.11, p = 0.03), while an initial intermediate viral load was associated with increased risk of inpatient mortality (OR 1.9, CI 1.14–3.21, p = 0.015) but not with increased risk for intubation.

Conclusion

The Ct value obtained from nasopharyngeal samples of hospitalized patients on admission may serve as a prognostic marker at an individual level and may help predict the course of the pandemic when evaluated at a population level.
A high-frequency single nucleotide polymorphism in the MtrB sensor kinase in clinical strains of Mycobacterium tuberculosis alters its biochemical and physiological properties
Authors: Waturuocha Uchenna Watson , P. J. Athira , Singh Krishna Kumar , Malhotra Vandana , Krishna M. S. , Saini Deepak Kumar
Published: September 2021

The DNA polymorphisms found in clinical strains ofMycobacterium tuberculosisdrive altered physiology, virulence, and pathogenesis in them. Although the lineages of these clinical strains can be traced back to common ancestor/s, there exists a plethora of difference between them, compared to those that have evolved in the laboratory. We identify a mutation present in ~80% of clinical strains, which maps in the HATPase domain of the sensor kinase MtrB and alters kinase and phosphatase activities, and affects its physiological role. The changes conferred by the mutation were probed byin-vitrobiochemical assays which revealed changes in signaling properties of the sensor kinase. These changes also affect bacterial cell division rates, size and membrane properties. The study highlights the impact of DNA polymorphisms on the pathophysiology of clinical strains and provides insights into underlying mechanisms that drive signal transduction in pathogenic bacteria.
Insulin management in hospitalized patients with diabetes mellitus on high-dose glucocorticoids: Management of steroid-exacerbated hyperglycemia
Authors: Cheng Yu-Chien , Guerra Yannis , Morkos Michael , Tahsin Bettina , Onyenwenyi Chioma , Fogg Louis , Fogelfeld Leon
Published: September 2021

Background

Glucocorticoid (GC)-exacerbated hyperglycemia is prevalent in hospitalized patients with diabetes mellitus (DM) but evidence-based insulin guidelines in inpatient settings are lacking.

Methods and findings

Retrospective cohort study with capillary blood glucose (CBG) readings and insulin use, dosed with 50% basal (glargine)-50% bolus (lispro) insulin, analyzed in hospitalized patients with insulin-treated DM given GC and matched controls without GC (n = 131 pairs). GC group (median daily prednisone-equivalent dose: 53.36 mg (IQR 30.00, 80.04)) had greatest CBG differences compared to controls at dinner (254±69 vs. 184±63 mg/dL, P<0.001) and bedtime (260±72 vs. 182±55 mg/dL, P<0.001). In GC group, dinner CBG was 30% higher than lunch (254±69 vs. 199±77 mg/dL, P<0.001) when similar lispro to controls given at lunch. Bedtime CBG not different from dinner when 20% more lispro given at dinner (0.12 units/kg (IQR 0.08, 0.17) vs. 0.10 units/kg (0.06, 0.14), P<0.01). Despite receiving more lispro, bedtime hypoglycemic events were lower in GC group (0.0% vs. 5.9%, P = 0.03).

Conclusions

Since equal bolus doses inadequately treat large dinner and bedtime GC-exacerbated glycemic excursions, initiating higher bolus insulin at lunch and dinner with additional enhanced GC-specific insulin supplemental scale may be needed as initial insulin doses in setting of high-dose GC.
HAV infection in Brazilian men who have sex with men: The importance of surveillance to avoid outbreaks
Authors: Castro Lisie Souza , Rezende Grazielli Rocha de , Pires Fernandes Fernanda Rodas , Bandeira Larissa Melo , Cesar Gabriela Alves , do Lago Barbara Vieira , Gomes Gouvêa Michele Soares , Motta-Castro Ana R. C.
Published: September 2021

Background

Hepatitis A is a fecal-oral infection caused by hepatitis A virus (HAV). Men who have sex with men (MSM) and transgender women (TW) have been reported as target groups for HAV infection. This study aimed to determine the seroprevalence, risk factors, and circulating strains associated with HAV infection among MSM and TW in Central Brazil.

Methods

A cross-sectional study was conducted from November 2011 to September 2013. Serum samples were collected from 425 individuals for anti-HAV antibody testing and HAV molecular characterization. Of them, 149 (35.1%) participants were self-identified as transgender women. Statistical analysis was performed to evaluate the risk factors of HAV seropositivity.

Results

The seroprevalence of HAV exposure was 69.7% (95% Confidence Interval: 65.3–74.0%). Serological evidence of HAV was significantly higher in participants who self-identified as transgender women (83.2%) than MSM (62.3%). Increasing age, non-white race, and lower monthly household income were independently associated with HAV exposure among MSM. Only lower monthly household income was independently associated with HAV exposure among TW. One anti-HAV IgM positive sample, from a transgender woman (0.2%), was detected and classified as subgenotype IA.

Conclusions

High HAV prevalence was observed, markedly among TW. Considering the risky sexual behaviors this population is exposed to, HAV vaccination and prevention programs targeting this population should be considered to prevent outbreaks and the burden of the disease.
Transcranial direct current stimulation (tDCS) enhances internal source monitoring abilities in healthy participants
Authors: Kusztrits Isabella , Marquardt Lynn , Hugdahl Kenneth , Hirnstein Marco
Published: September 2021

Source monitoring refers to the ability to identify the origin of a memory, for example, whether you remember saying something or thinking about it, and confusions of these sources have been associated with the experience of auditory verbal hallucinations (AVHs). Both AVHs and source confusions are reported to originate from dysfunctional brain activations in the prefrontal cortex (PFC) and the superior temporal gyrus (STG); specifically, it is assumed that a hypoactive PFC and a hyperactive STG gives rise to AVHs and source confusions. We set out to test this assumption by trying to mimic this hypertemporal/hypofrontal model in healthy individuals with transcranial direct current stimulation (tDCS): the inhibitory cathode was placed over the left PFC and the excitatory anode over the left dorsolateral STG. Participants completed a reality monitoring task (distinguishing between external and internal memory sources) and an internal source monitoring task (distinguishing between two or more internal memory sources) in two separate experiments (offline vs. online tDCS). In the offline experiment (n = 34), both source monitoring tasks were completed after tDCS stimulation, and in the online experiment (n = 27) source monitoring tasks were completed while simultaneously being stimulated with tDCS. We found that internal source monitoring abilities were significantly enhanced during active online tDCS, while reality monitoring abilities were unaffected by stimulation in both experiments. We speculate, based on combining the present findings with previous studies, that there might be different brain areas involved in reality and internal source monitoring. While internal source monitoring seems to involve speech production areas, specifically Broca’s area, as suggested in the present study, reality monitoring seems to rely more on the STG and DLPFC, as shown in other studies of the field.
5-year outcomes of single iStent (G1) trabecular microbypass implantation with phacoemulsification in moderately advanced primary open angle glaucoma
Authors: Ansari Ejaz
Published: September 2021

Purpose

To evaluate the safety and efficacy of combined phacoemulsification and single iStent (G1) (iStent, Glaukos Corp. San Clemente, USA), implantation in moderately advanced primary open angle glaucoma (POAG) with 5-years follow-up.

Methods

Retrospective, interventional case series. All subjects had POAG and underwent single iStent implantation+ phaco+IOL by a single surgeon, with 5 years follow-up. Primary outcome measures: reduction in intraocular pressure (IOP) and proportion of eyes achieving at least 20% reduction of IOP at 5 years. Secondary outcome measures: number of glaucoma drops at 1 through to 5 years; change in visual field mean deviation (MD) at year 5 compared to baseline.

Results

35 eyes of 26 patients were included. Mean (sd) medicated pre-op IOP was 18.5 (3.2) mm Hg on mean (sd) 2.3 (1.0) medications. Mean IOP was reduced to 15.9 (4.5) mm Hg on 2.2 (0.9) drops, 15.0mm (4.5) mm Hg on 2.3 (0.9) drops, 15.6 (3.6) mm Hg on 2.5 (1.0) drops, 15.7 (4.43) mmHg on 2.6 (1.0) drops and 14.7 (3.02) mmHg (P<0.001) on 2.7 (1.14) drops (P = 0.06) from 1 through to 5 years. At year 5, 62% of eyes had achieved at least 20% reduction in IOP. MD reduced from -8 (8.1) dB to -10.7 (13.4) dB over 5 years (p = 0.8) at 0.54dB/ annum. One eye required filtering surgery. There were no sight-threatening complications.

Conclusion

This study showed sustained IOP reduction and excellent safety profile for single iStent implantation. Uniquely it provides data for a more severe stage of glaucoma, and also visual field data, which indicated no significant change through 5 years.
The multi-channel potentiostat: Development and evaluation of a scalable mini-potentiostat array for investigating electrochemical reaction mechanisms
Authors: Pansodtee Pattawong , Selberg John , Jia Manping , Jafari Mohammad , Dechiraju Harika , Thomsen Thomas , Gomez Marcella , Rolandi Marco , Teodorescu Mircea
Published: September 2021

A potentiostat is an essential piece of analytical equipment for studying electrochemical devices and reactions. As the design of electrochemical devices evolve, applications for systems with multiple working electrodes have become more common. These applications drive a need for low-cost multi-channel potentiostat systems. We have developed a portable, low-cost and scalable system with a modular design that can support 8 to 64 channels at a cost as low as $8 per channel. This design can replace the functionality of commercial potentiostats which cost upwards of $10k for certain applications. Each channel in the multi-channel potentiostat has an independent adjustable voltage source with a built-in ammeter and switch, making the device flexible for various configurations. The multi-channel potentiostat is designed for low current applications (nA range), but its purpose can change by varying its shunt resistor value. The system can either function as a standalone device or remotely controlled. We demonstrate the functionality of this system for the control of a 24-channel bioelectronic ion pump for open- and closed- loop control of pH.
A comprehensive integrated post-GWAS analysis of Type 1 diabetes reveals enhancer-based immune dysregulation
Authors: Kim Seung-Soo , Hudgins Adam D. , Yang Jiping , Zhu Yizhou , Tu Zhidong , Rosenfeld Michael G. , DiLorenzo Teresa P. , Suh Yousin
Published: September 2021

Type 1 diabetes (T1D) is an organ-specific autoimmune disease, whereby immune cell-mediated killing leads to loss of the insulin-producing β cells in the pancreas. Genome-wide association studies (GWAS) have identified over 200 genetic variants associated with risk for T1D. The majority of the GWAS risk variants reside in the non-coding regions of the genome, suggesting that gene regulatory changes substantially contribute to T1D. However, identification of causal regulatory variants associated with T1D risk and their affected genes is challenging due to incomplete knowledge of non-coding regulatory elements and the cellular states and processes in which they function. Here, we performed a comprehensive integrated post-GWAS analysis of T1D to identify functional regulatory variants in enhancers and their cognate target genes. Starting with 1,817 candidate T1D SNPs defined from the GWAS catalog and LDlink databases, we conducted functional annotation analysis using genomic data from various public databases. These include 1) Roadmap Epigenomics, ENCODE, and RegulomeDB for epigenome data; 2) GTEx for tissue-specific gene expression and expression quantitative trait loci data; and 3) lncRNASNP2 for long non-coding RNA data. Our results indicated a prevalent enhancer-based immune dysregulation in T1D pathogenesis. We identified 26 high-probability causal enhancer SNPs associated with T1D, and 64 predicted target genes. The majority of the target genes play major roles in antigen presentation and immune response and are regulated through complex transcriptional regulatory circuits, including those in HLA (6p21) and non-HLA (16p11.2) loci. These candidate causal enhancer SNPs are supported by strong evidence and warrant functional follow-up studies.
The effects of cholesterol accumulation on Achilles tendon biomechanics: A cross-sectional study
Authors: Squier Kipling , Scott Alexander , Hunt Michael A. , Brunham Liam R. , Wilson David R. , Screen Hazel , Waugh Charlie M.
Published: September 2021

Familial hypercholesterolemia, a common genetic metabolic disorder characterized by high cholesterol levels, is involved in the development of atherosclerosis and other preventable diseases. Familial hypercholesterolemia can also cause tendinous abnormalities, such as thickening and xanthoma (tendon lipid accumulation) in the Achilles, which may impede tendon biomechanics. The objective of this study was to investigate the effect of cholesterol accumulation on the biomechanical performance of Achilles tendons, in vivo. 16 participants (10 men, 6 women; 37±6 years) with familial hypercholesterolemia, diagnosed with tendon xanthoma, and 16 controls (10 men, 6 women; 36±7 years) underwent Achilles biomechanical assessment. Achilles biomechanical data was obtained during preferred pace, shod, walking by analysis of lower limb kinematics and kinetics utilizing 3D motion capture and an instrumented treadmill. Gastrocnemius medialis muscle-tendon junction displacement was imaged using ultrasonography. Achilles stiffness, hysteresis, strain and force were calculated from displacement-force data acquired during loading cycles, and tested for statistical differences using one-way ANOVA. Statistical parametric mapping was used to examine group differences in temporal data. Participants with familial hypercholesterolemia displayed lower Achilles stiffness compared to the control group (familial hypercholesterolemia group: 87±20 N/mm; controls: 111±18 N/mm; p = 0.001), which appeared to be linked to Achilles loading rate rather than an increased strain (FH: 5.27±1.2%; controls: 4.95±0.9%; p = 0.413). We found different Achilles loading patterns in the familial hypercholesterolemia group, which were traced to differences in the centre of pressure progression that affected ankle moment. This finding may indicate that individuals with familial hypercholesterolemia use different Achilles loading strategies. Participants with familial hypercholesterolemia also demonstrated significantly greater Achilles hysteresis than the control group (familial hypercholesterolemia: 57.5±7.3%; controls: 43.8±10%; p<0.001), suggesting that walking may require a greater metabolic cost. Our results indicate that cholesterol accumulation could contribute to reduced Achilles function, while potentially increasing the chance of injury.
Service user experiences and views regarding telemental health during the COVID-19 pandemic: A co-produced framework analysis
Authors: Vera San Juan Norha , Shah Prisha , Schlief Merle , Appleton Rebecca , Nyikavaranda Patrick , Birken Mary , Foye Una , Lloyd-Evans Brynmor , Morant Nicola , Needle Justin J. , Simpson Alan , Lyons Natasha , Rains Luke Sheridan , Dedat Zainab , Johnson Sonia
Published: September 2021

Background

The prominence of telemental health, including providing care by video call and telephone, has greatly increased during the COVID-19 pandemic. However, there are clear variations in uptake and acceptability, and concerns that digital exclusion may exacerbate previous inequalities in access to good quality care. Greater understanding is needed of how service users experience telemental health, and what determines whether they engage and find it acceptable.

Methods

We conducted a collaborative framework analysis of data from semi-structured interviews with a sample of people already experiencing mental health problems prior to the pandemic. Data relevant to participants’ experiences and views regarding telemental health during the pandemic were identified and extracted. Data collection and analysis used a participatory, coproduction approach where researchers with relevant lived experience, contributed to all stages of data collection, analysis and interpretation of findings alongside clinical and academic researchers.

Findings

The experiences and preferences regarding telemental health care of the forty-four participants were dynamic and varied across time and settings, as well as between individuals. Participants’ preferences were shaped by reasons for contacting services, their relationship with care providers, and both parties’ access to technology and their individual preferences.

While face-to-face care tended to be the preferred option, participants identified benefits of remote care including making care more accessible for some populations and improved efficiency for functional appointments such as prescription reviews. Participants highlighted important challenges related to safety and privacy in online settings, and gave examples of good remote care strategies they had experienced, including services scheduling regular phone calls and developing guidelines about how to access remote care tools.

Discussion

Participants in our study have highlighted advantages of telemental health care, as well as significant limitations that risk hindering mental health support and exacerbate inequalities in access to services. Some of these limitations are seen as potentially removable, for example through staff training or better digital access for staff or service users. Others indicate a need to maintain traditional face-to-face contact at least for some appointments. There is a clear need for care to be flexible and individualised to service user circumstances and preferences. Further research is needed on ways of minimising digital exclusion and of supporting staff in making effective and collaborative use of relevant technologies.
Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression
Authors: Hu Qi-Xin , Wang Hui-Yi , Jiang Lu , Wang Chen-Yu , Ju Lin-Gao , Zhu Yuan , Zhong Bo , Wu Min , Wang Zhen , Li Lian-Yun
Published: September 2021

Under RNA virus infection, retinoic acid-inducible gene I (RIG-I) in host cells recognizes viral RNA and activates the expression of type I IFN. To investigate the roles of protein methyltransferases and demethylases in RIG-I antiviral signaling pathway, we screened all the known related enzymes with a siRNA library and identified LSD1 as a positive regulator for RIG-I signaling. Exogenous expression of LSD1 enhances RIG-I signaling activated by virus stimulation, whereas its deficiency restricts it. LSD1 interacts with RIG-I, promotes its K63-linked polyubiquitination and interaction with VISA/MAVS. Interestingly, LSD1 exerts its function in antiviral response not dependent on its demethylase activity but through enhancing the interaction between RIG-I with E3 ligases, especially TRIM25. Furthermore, we provide in vivo evidence that LSD1 increases antiviral gene expression and inhibits viral replication. Taken together, our findings demonstrate that LSD1 is a positive regulator of signaling pathway triggered by RNA-virus through mediating RIG-I polyubiquitination.
Dreams and desire. The cinema of Pier Paolo Pasolini and Federico Fellini: A conversation with Roberto Chiesi
Authors: Porcarelli Angela
Published: September 2021

In this interview, Roberto Chiesi talks about the personal and professional relationship between Pier Paolo Pasolini and Federico Fellini. He describes their experience with neorealism and how each of them moved past it to develop an original and unique cinematographic style. He focuses on specific elements of their cinema, such as the importance of the oneiric dimension and their conception of the sacred. Chiesi explains the central role civic involvement had in the work of Pasolini; his last movie Salò o le 120 giornate di Sodoma (Salò, or the 120 Days of Sodom) () is centred on the dramatic process of degradation caused by the new consumeristic ideology. Fellini, instead, was primarily concerned with the corruptive vulgarity of the new commercial television. Highlighting the importance of Pasolini and Fellini’s legacy, Chiesi concludes the interview by saying that the two artists had the foresight to imagine the dreadful long-term consequences the events of their time would produce, consequences we are experiencing in today’s society.
Responsibly Including Survivors’ Voices in the Planning and Implementing of Educational Programmes for Healthcare Providers
Authors: Panda Preeti , Mango Annette , Garg Anjali
Published: September 2021

Survivors’ experiences and input are essential for human trafficking education for healthcare providers yet they remain under-utilised. This article describes a collaborative initiative between two paediatric physicians and a survivor of trafficking, which led to the implementation of an anti-trafficking education programme for healthcare providers. It outlines the process of establishing the collaboration and the main principles of ensuring an equitable partnership. It shares the authors’ reflections of the process and their recommendations for others seeking to establish similar initiatives.
Identities in Roman Macedonia during the Early Imperial Period
Authors: Murray Sheanna
Published: September 2021

This paper focuses on the impact of the Roman presence in Macedonia on the collective identities of the local population from the beginning of Roman rule in the region in 167 BC until the early 3rd century AD. The societal changes taking place during the first three and a half centuries have been outlined using the available epigraphic, numismatic and onomastic evidence to analyse the evolving identities of the Macedonians and the new forms of expression of these identities. The approach taken in this paper is not one of Hellenisation or Romanisation but of acculturation, focussing on the identities of the Macedonian people that adapted and evolved in relation to the new political and cultural environment.
The Silent Revolution: The Roman Army between Polybius and Marius
Authors: Biglino Fabrizio
Published: September 2021

Traditionally, Polybius’ description of the Roman army in Book VI of his Histories is considered the de facto image of the mid-Republican Roman legions until the major changes introduced by the reforms attributed to Gaius Marius. However, there are several elements highlighting the fact that Polybius’ description actually depicts a rather outdated military system, making it hard to accept it as an up-to-date portrait of the army by the mid-second century. By examining hints within the sources, this paper aims to proper examine the major variations that interested the Roman military system from the mid-third to the late second centuries and to highlight their overall impact.
CD3+/CD4+/CD5+/CD8+/CD21+/CD34-/CD45-/CD79a-/TCRαβ+/TCRγδ-/MHCII+ T-zone lymphoma in a dog with generalized lymphadenopathy: a case report
Authors: Shin Sun Woo , Lim Yu jin , Bae Hyeona , Kim Jihu , Cho ARom , Park Jinho , Lee Dongbin , Jung Dong-In , Kim Sang-ki , Yu DoHyeon
Published: September 2021

Canine T-zone lymphoma (TZL) is a mature T-cell lymphoma in dogs. The diagnosis and sub-classification are impossible without biopsy or immunophenotyping by flow cytometry. An 11-year-old, spayed, female Golden Retriever presented with lymph node enlargement. Clinical examination was consistent with canine multicentric lymphoma. However, immunophenotyping revealed positive for CD3, CD4, CD5, CD8, CD21, TCRαβ, and MHCII but negative for CD34, CD45, CD79a, and TCRγδ. Histopathology revealed lymphocytes expanding to the cortex-preserving architecture and thinning of the nodal capsule, and CD3 positive but PAX-5 negative. Owing to the indolent nature of TZL, careful monitoring approach without clinical intervention was utilized.
Microbiota markers level in the cerebrospinal fluid of patients with multiple sclerosis and radiologically isolated syndrome
Authors: Boyko A. N. , Melnikov M. V. , Boyko O. V. , Kabaeva A. R. , Omarova M. A. , Zhilenkova O. G. , Zatevalov A. M. , Rogovskii V. S.
Published: September 2021

According to numerous studies, gut microbiota plays a significant role in multiple sclerosis (MS) development. However, data on changes in the gut microbiota in MS is often contradictory. The most common approach in gut microbiota research is the 16S ribosomal RNA sequencing of fecal microbiota. However, such data do not reflect the composition of the entire body microbiota. There is also a lack of data on microbiota markers in the cerebrospinal fluid (CSF) of patients with MS and predisposing conditions.

Objective: to assess the level of microbial markers in the CSF of patients with MS and radiologically isolated syndrome (RIS).

Patients and methods. We used gas chromatography-mass spectrometry (GC-MS) to evaluate microbial markers levels in eight patients with MS, five patients with RIS, and seven controls.

Results and discussion. We found an increase in microbial load in patients with MS, indicating a possible association of MS with polymicrobial infection. In particular, an increase in the content of Streptococcus markers was observed, as well as a tendency to a three-fold increase in the campesterol content (a marker of campesterol-producing microfungi) in the CSF of patients with MS, compared to the control group (diagnostic punctures, various diseases of the nervous system of a non-autoimmune or inflammatory nature, not acute states).

Conclusion. GC-MS of microbial markers can be used to assess the presence of microbial markers in the CSF. The CSF of patients with MS contains an increased amount of various microbial markers, which may indicate a possible association of MS with polymicrobial infection.
From Textuality to Universality: The Evolution of Ḥirābah Crimes in Islamic Jurisprudence
Authors: Khasan Moh
Published: September 2021

The issue of the escalation of crime, which is increasingly varied and is getting heavier, is becoming a global concern. The development and progress of the world seems to have contributed to changes in the type and quality of crime, not only in the form and method, but also in the damage it causes. Crime trends increasingly point to collective crimes, systematic crimes, and crimes with extensive and massive excess damage. This article intends to criticize the systematic change (evolution) that has occurred in the concept of ḥirābah crime in Islamic law from a classical to contemporary perspective. The qualitative analysis of this article is focused on three fundamental issues, namely; ḥirābah interpretation, ḥirābah liability, and ḥirābah punishment. The author reveals in the conclusion that; first, based on its elements and characteristics, the definition of ḥirābah can be expanded to include new types of crimes such as; terrorism, rape, and drug trafficking and smuggling. Second, it is necessary to reconstruct the ḥirābah responsibility theory into a formulation that considers the principle of legal certainty and the principle of equality before the law. The reconstruction model, among others, is the affirmation that all people who involve themselves in the crime are perpetrators of ḥirābah (with an ishtirāk approach). Likewise, reconstruction efforts are needed to enforce equality of accountability between male and female actors. Third, as a serious crime, ḥirābah deserves a severe punishment and has a strong deterrent effect, as offered by Islamic law. However, the opportunity to give dispensation to the punishment will always be open if the perpetrator can prove his seriousness in repenting.[Eskalasi kriminalitas yang semakin beragam dan berat telah menjadi perhatian global saat ini. Pembangunan dan kemajuan dunia berkontribusi pada perubahan pola dan tingkat kriminalitas, tidak hanya bentuk dan cara, tetapi juga akibat yang ditimbulkan. Trend kriminalitas bertambah mulai dari yang berkelompok, sistematis, hingga yang kerusakannya masif dan pengaruhnya panjang. Tulisan ini mengkritisi perubahan sistematis pada konsep kriminal (ḥirābah) dalam hukum Islam dari pendekatan klasik hingga kontemporer. Analisis kualitatif dalam tulisan ini fokus pada tiga hal mendasar yaitu penafsiran, arah kecenderungan dan hukuman. Kesimpulan pertama tulisan ini adalah definisi kriminal berdasarkan unsur dan karakternya yang dapat meluas maknanya termasuk terorisme, pemerkosaan, narkoba, dan penyelundupan. Kedua, perlu rekonstruksi baru teori kriminalitas yang mempertimbangkan kepastian hukum dan kesetaraan hak dimuka hukum. Ketiga, sebagai kejahatan serius, ḥirābah pantas mendapat hukuman berat dan mempunyai efek pencegahan yang kuat seperti halnya dalam hukum Islam. Meski demikian, ada peluang dispensasi hukuman jika pelaku dapat menunjukkan kesungguhan untuk bertobat.]
The Writing of Hadith in the Era of Prophet Muhammad: A Critique on Harun Nasution’s Thought
Authors: Harun Daud Rasyid , Rasyid Aisyah Daud , Lubis Asmuliadi , Mohd Balwi Mohd Abd Wahab Fatoni Bin , Rasyid Bilal Daud
Published: September 2021

The discussion regarding the writing of hadith during the life of the Prophet is a contentious topic within the area of Islamic and hadith studies both in the West and in the Islamic world. Orientalists write their work on hadith with a presumption that hadith has never been written during the life of Prophet Muḥammad. They contend that hadith text only emerged in the third century of Hijrah, i.e. in the era of al-Bukhāri. A few others believe that it started in the era of Malik of the Umayyad. This orientalist’ mindset affects some Muslim intellectuals who accept this premise. One of them is Harun Nasution, a well respected great mind who wrote a book entitled Islam Ditinjau Dari Berbagai Aspeknya (Islam Viewed from Various Aspects). However, historical evidence demonstrates that the writing of hadith was carried out at the time when the Prophet was still alive. A number of sheets were discovered, which contain hadith text compilations narrated by the companions of the Prophet, such as the Ṣahīfah of  ͑Ali bin Abi Ṭalib, Ṣahifah of Jābir bin  ͑Abdillah, and others. Some scholars have misunderstood the message in a saying of the Prophet that prohibited the writing of hadith. They have ignored other hadith that negated the previous hadith by which the Prophet allowed the writing of hadith in his life time. Even though there are a number companions who did not write hadith in this period, it does not mean hadith were not allowed to be written, but it was due to their own preference not to write the hadith.[Perdebatan tentang penulisan hadits masa kehidupan Nabi tetap menjadi tema yang hangat dalam kajian keislaman dan kajian hadits, baik di barat maupun di dunia Islam sendiri. Beberapa orientalis berpendapat bahwa hadits tidak ditulis pada masa Nabi Muhammad. Mereka menyebutkan teks hadits mulai muncul abad ketiga hijriah, misalnya pada era Bukhari. Lainnya percaya bahwa teks hadits dimulai pada masa Malik al Umayyad. Perspektif seperti orientalis ini diterima oleh beberapa intelektual muslim Indonesia, salah satunya Harun Nasution yang menulis buku Islam ditinjau dari Berbagai Aspeknya. Bagaimanapun bukti sejarah menunjukkan penulisan hadits sudah dimulai ketika Nabi masih hidup. Sejumlah lembaran yang mengandung kompilasi teks hadits dari beberapa sahabat Nabi seperti, Ṣahīfah dari Ali bin Abi Ṭalib dan Ṣahifah dari Jābir bin  ͑Abdillah. Sejumlah akademisi keliru dalam memahami pesan Nabi yang melarang menuliskan hadits. Mereka mengabaikan hadits yang menegasikan hadits sebelumnya yang membolehkan penulisan hadits selama hidup Nabi. Meskipun ada sejumlah sahabat yang melarangnya, namun ini bukan berarti hadits tidak diijinkan untuk ditulis, tetapi hal ini lebih terkait dengan masing-masing referensi untuk tidak menuliskannya.]
Stuck in Sharia Space: The Experiences of Christian Students to Reside in Langsa, Aceh
Authors: Febriandi Yogi , Amri Yaser
Published: September 2021

This article examines the problem of spatial access for Christian students of Samudera University as experiences of minorities in Langsa, Aceh. This article argues that Aceh’s public space that is formed by religious identity, leads dichotomy of citizenship in social life. Using life story method, this article explores the problem of Christian students of Samudera University to reside in Langsa. The results show the formation of space by displaying a single identity has polarized majority-minority in public space. Finally, this article also shows that the formation of space by displaying a single identity created an imbalance space for minority, and compelling minority to create alternative space.[Artikel ini membahas persoalan akses ruang berdasarkan pengalaman mahasiswa minoritas Kristen di Universitas Samudera, Langsa, Aceh. Artikel ini berargumentasi bahwa ruang publik Aceh terbentuk oleh identitas religius yang berujung pada dikotomi kehidupan sosial penduduknya. Dengan pendekatan life story, artikel ini menjelaskan masalah yang dihadapi mahasiswa Kristen yang tinggal di Langsa, Aceh. Dalam kesimpulannya menunjukkan bahwa formasi ruang publik terbelah dan tidak seimbang antara identitas mayoritas dan minoritas, dimana identitas minoritas terdesak untuk menciptakan ruang alternatif baru.]
Islam and Humanity: Commodification of Aid for Rohingya in Aceh
Authors: Darnela Lindra
Published: September 2021

This study examines how Rohingya refugees in Aceh in 2015-2016 received assistance and the role of Islamic philanthropic institutions in providing aid. The paper shows that through the media, Islamic philanthropic institutions have successfully advocated for Rohingya rights and raised the issue as a religious issue so that they have collected large donations. Also, this paper finds a discrepancy between the information conveyed by the media and the reality in the field, showing significant efforts in the commodification of humanitarian aid and abuse of religion.[Artikel ini membahas bagaimana pengungsi Rohingya di Aceh periode 2015-2016 mendapatkan bantuan dan peran dari lembaga filantropi Islam dalam penyediaan bantuan tersebut. Artikel ini menjelaskan bahwa lembaga filantrofi Islam berhasil mengadvokasi hak Rohingya melalui media dan mengkaitkan dalam isu agama sehingga mendapatkan donasi yang berlipat. Selain itu dalam artikel ini juga menunjukkan ketidaksesuaian antara informasi di media dengan kenyataan di lapangan, bahkan terdapat indikasi komodifikasi bantuan kemanusiaan dan penyalahgunaan agama.]