Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolving Status of Clinical Immunotherapy with Oncolytic Adenovirus

Cancer immunotherapy targeting immune checkpoint inhibitors shows efficacy in several human cancers, but “cold tumors” that lack immune cells are typically unresponsive. Among the potential therapeutic approaches that could “heat” or promote lymphocyte infiltration of cold tumors, oncolytic viruses have attracted interest for their lytic and immunogenic mechanisms of action. In this article, we review the use of oncolytic adenoviruses in cancer immunotherapy, with a particular focus on preclinical and clinical data of oncolytic adenovirus-triggered immune responses against tumor antigens. We also discuss parameters to consider in clinical trial design and the combination of oncolytic adenoviruses with conventional treatments or other immunotherapies.
The design basis for the integrated and continuous biomanufacturing framework

An 8 ton per year manufacturing facility is described based on the framework for integrated and continuous bioprocessing (ICB) common to all known biopharmaceutical implementations. While the output of this plant rivals some of the largest fed‐batch plants in the world, the equipment inside the plant is relatively small: the plant consists of four 2000 L single‐use bioreactors and has a maximum flow rate of 13 L/min. The equipment and facility for the ICB framework is described in sufficient detail to allow biopharmaceutical companies, vendors, contract manufacturers to build or buy their own systems. The design will allow the creation of a global ICB ecosystem that will transform biopharmaceutical manufacturing. The design is fully backward compatible with legacy fed‐batch processes. A clinical production scale is described that can produce smaller batch sizes with the same equipment as that used at the commercial scale. The design described allows the production of as little as 10 g to nearly 35 kg of drug substance per day.
„Der Mensch, der Handball spielt, braucht den Ball, den Kontakt und die Gemeinschaft“ – Veränderungen im Sportangebot durch die COVID-19 Pandemie und deren Bedeutung für Sportvereine

Zusammenfassung Ziel der Studie Sportvereine spielen eine wichtige Rolle für die Bewegungs- und damit auch die Gesundheitsförderung in Deutschland. Die vorliegende Studie befasst sich vor dem Hintergrund der Corona-bedingten Einschränkungen mit den Veränderungen in der Angebotsstruktur und deren Bedeutung für die Sportvereine. Methode Es wurden 15 Experteninterviews mit Vertretern und Vertreterinnen bayerischer Sportvereine geführt. Die Daten wurden transkribiert und mittels thematischer Analyse induktiv ausgewertet. Ergebnisse Von den Vereinen wurden umfangreiche Aktivitäten entwickelt, um den Mitgliedern auch unter den Rahmenbedingungen der COVID-19-Pandemie Möglichkeiten für sportliche Aktivitäten zu bieten. Die Vereinsmitglieder hätten dabei mit viel Verständnis auf die Veränderungen und Einschränkungen im Angebot reagiert. Die Nutzung der neu geschaffenen digitalen Angebote durch die Mitglieder scheint sich von der Nutzung der realen Kurse zu unterscheiden. Das längerfristige Potenzial der digitalen Angebote wird jedoch weitgehend skeptisch betrachtet. Insbesondere der im Sport normalerweise immanente Gemeinschaftsaspekt würde den Teilnehmenden an digitalen Formaten fehlen. Schlussfolgerungen Die Anstrengungen der Sportvereine, ein geregeltes Bewegungsprogramm auch unter den Rahmenbedingungen einer Pandemie bereit zu stellen, betont deren Bedeutung für Prävention und Gesundheitsförderung. Aus Public-Health-Sicht bieten die Veränderungen in der Angebotsstruktur darüber hinaus das Potenzial, auch unter normalisierten Rahmenbedingungen beibehalten zu werden. Hierzu sind aber weiterführende Forschungsarbeiten notwendig.
Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin

Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions.
Molecular Characterization and Genetic Diversity of Haplogroup E Human Lice in Guinea, West Africa

Pediculus humanus capitis, the head louse, is an obligate blood-sucking ectoparasite that occurs in six divergent mitochondrial clades (A, D, B, F, C and E). Several studies reported the presence of different pathogenic agents in head lice specimens collected worldwide. These findings suggest that head louse could be a dangerous vector and a serious public health problem. Herein, we aimed to study the mitochondrial genetic diversity, the PHUM540560 gene polymorphisms profile of head lice collected in Guinea, as well as to screen for their associated pathogens. In 2018, a total of 155 head lice were collected from 49 individuals at the Medicals Centers of rural (Maférinyah village) and urban (Kindia city) areas, in Guinea. Specimens were subjected to a genetic analysis and pathogens screening using molecular tools. Results showed that all head lice belonged to eight haplotypes in the E haplogroup, with six newly identified for the first time. The study of the PHUM540560 gene polymorphisms of our clade E-head lice revealed that 82.5% exhibited the same polymorphism profile as the previously reported clade A-body lice. Screening for targeted pathogens revealed the presence of Acinetobacter spp. , while sequencing highlighted the presence of several species, including Acinetobacter baumannii, Acinetobacter nosocomialis, Acinetobacter variabilis, Acinetobacter towneri and for the first time Acinetobacter haemolyticus. Our study is the first to report the existence of the Guinean haplogroup E, the PHUM540560 gene polymorphism profile as well as the presence of Acinetobacter species in head lice collected from Guinea.
Therapeutic benefits of pharmacologic and nonpharmacologic treatments for depressive symptoms after traumatic brain injury: a systematic review and network meta-analysis

Background Depression is a common morbidity after traumatic brain injury. This network meta-analysis investigated the efficacy and tolerability of pharmacologic and nonpharmacologic interventions for depression after traumatic brain injury. Methods We extracted randomized controlled trials examining pharmacologic or nonpharmacologic interventions with placebo- or active-controlled designs from PubMed, the Cochrane Library and ScienceDirect, from inception to October 30, 2018. We based study selection and extraction of a pre-defined list of variables on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, and conducted meta-analysis procedures using random effects modelling. Primary outcomes were changes in depressive symptom severity after pharmacologic or nonpharmacologic treatment; the secondary outcome was tolerability, reflected in overall patient dropout rates. Results Our analysis of 27 randomized controlled trials (10 pharmacologic, total n = 483, mean age = 37.9 yr; 17 nonpharmacologic, total n = 1083, mean age = 38.0 yr) showed that methylphenidate had significantly superior efficacy compared to placebo or control (standardized mean difference −0.91, 95% confidence interval [CI] −1.49 to −0.33). Sertraline was associated with significantly lower tolerability (i.e., a higher dropout rate) compared to placebo or control (odds ratio 2.65, 95% CI 1.27 to 5.54). No nonpharmacologic treatment was more effective than the others, and we found no significant differences in tolerability (i.e., dropout rates) among the nonpharmacologic treatments. Limitations Heterogeneity in participant characteristics (e.g., comorbidities), study designs (e.g., trial duration) and psychopathology assessment tools, as well as small trial numbers for some treatment arms, could have been confounders. Conclusion The present network meta-analysis suggests that methylphenidate might be the best pharmacologic intervention for depressive symptoms related to traumatic brain injury. None of the nonpharmacologic interventions was associated with better improvement in depressive symptoms than the others or than control conditions. None of the pharmacologic or nonpharmacologic treatments had inferior tolerability compared to placebo or controls except for sertraline, which had significantly lower tolerability than placebo.
Voice of the Victims: Accounts of Secondary Victimization With the Court System Among Homicide Co-victims

The treatment homicide co-victims receive from the criminal justice system often leaves them aggrieved and feeling alienated. A neglected but important area of investigation is the courtroom workgroup’s handling of murder cases. This exploratory study examines the nature and extent to which varying secondary victimization experiences are common among co-victims as the murder cases are processed through the court system. The sample consists of 27 co-victims connected to 24 separate cases where the murders occurred in a major metropolitan area in the southeastern United States. Drawing upon focus group data, Nvivo 10 was employed to identify themes that illustrate common secondary victimization experiences among co-victims along with positive and mixed reactions to court processes and personnel. The findings indicate that court requirements to provide notifications are infrequently met and attorney’s practice to supply information about case progress and counseling to family members regarding plea-bargaining and sentencing decisions are greatly restrictive. When information is offered, it is often perceived as highly technical and when assistance is provided, it is frequently limited or intermittent. Despite the prevalence of negative experiences, there also were reports of positive interactions with the district attorney and victim advocates. The study concludes by identifying ways in which the courtroom workgroup can uphold the rights afforded to co-victims while at the same time meeting the duties and responsibilities of the workgroup.
Anoxygenic photo- and chemo-synthesis of phototrophic sulfur bacteria from an alpine meromictic lake

ABSTRACT Meromictic lakes are interesting ecosystems to study anaerobic microorganisms due their permanent stratification allowing the formation of a stable anoxic environment. The crenogenic meromictic Lake Cadagno harbors an important community of anoxygenic phototrophic sulfur bacteria responsible for almost half of its total productivity. Besides their ability to fix CO2 through photosynthesis, these microorganisms also showed high rates of dark carbon fixation via chemosyntesis. Here, we grew in pure cultures three populations of anoxygenic phototrophic sulfur bacteria previously isolated from the lake, accounting for 72.8% of the total microbial community and exibiting different phenotypes: (1) the motile, large-celled purple sulfur bacterium (PSB) Chromatium okenii, (2) the small-celled PSB Thiodictyon syntrophicum and (3) the green sulfur bacterium (GSB) Chlorobium phaeobacteroides. We measured their ability to fix CO2 through photo- and chemo-synthesis, both in situ in the lake and in laboratory under different incubation conditions. We also evaluated the efficiency and velocity of H2S photo-oxidation, an important reaction in the anoxygenic photosynthesis process. Our results confirm that phototrophic sulfur bacteria strongly fix CO2 in the presence of light and that oxygen increases chemosynthesis at night, in laboratory conditions. Moreover, substancial differences were displayed between the three selected populations in terms of activity and abundance.
Autoimmune and Chronic Inflammatory Disease Patients with COVID‐19

There are limited data on the impact of coronavirus disease 2019 (COVID‐19) on hospitalized patients with autoimmune and chronic inflammatory disease (AICID) compared with patients who do not have AICID. We sought to evaluate whether patients with AICID who have confirmed COVID‐19 presenting to the hospital are at higher risk of adverse outcomes compared with those patients without AICID who are infected with COVID‐19 and whether immunosuppressive medications impact this risk.
Anterior cingulate gyrus acts as a moderator of the relationship between problematic mobile phone use and depressive symptoms in college students

Abstract This study aimed to investigate the brain grey matter volume (GMV) related to problematic mobile phone use (PMPU), and whether these regions of GMV play a potential moderating role in the relationship between PMPU and depressive symptoms. We recruited 266 students who underwent magnetic resonance imaging (MRI) scanning. PMPU and depressive symptoms were assessed by a self-rating questionnaire for adolescent PMPU and patient health questionnaire-9, respectively. A multiple regression model was performed to detect GMV and white matter (WM) integrity associated with PMPU by voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) methods, and the moderating analysis was conducted by PROCESS using SPSS software. VBM analysis found an inverse correlation between the GMV of the anterior cingulate gyrus (ACC) and right fusiform gyrus (FFG) with PMPU (PFDR < 0.05), and TBSS analysis revealed that fractional anisotropy (FA) in the body of the corpus callosum was negatively correlated with PMPU. The correlation between PMPU and depressive symptoms was moderated by the GMV of the ACC. These results suggest that the GMV of the ACC and right FFG, as well as FA in the body of the corpus callosum, was related to PMPU, and we further found that increased GMV of the ACC could reduce the relationship between PMPU and depressive symptoms in college students.
16Up: Outline of a Study Investigating Wellbeing and Information and Communication Technology Use in Adolescent Twins

Abstract The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.
Repeated Dose Toxicity Study and Developmental and Reproductive Toxicology Studies of a Respiratory Syncytial Virus Candidate Vaccine in Rabbits and Rats

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections, and vaccines are needed to treat young children and older adults. One of GSK’s candidate vaccines for RSV contains recombinant RSVPreF3 protein maintained in the prefusion conformation. The differences in immune function of young children and older adults potentially require different vaccine approaches. For young children, anti-RSV immunity can be afforded during the first months of life by vaccinating the pregnant mother during the third trimester with unadjuvanted RSVPreF3, which results in protection of the infant due to the transplacental passage of anti-RSV maternal antibodies. For older adults with a waning immune response, the approach is to adjuvant the RSVPreF3 vaccine with AS01 to elicit a more robust immune response. The local and systemic effects of biweekly intramuscular injections of the RSVPreF3 vaccine (unadjuvanted, adjuvanted with AS01, or coadministered with a diphtheria-tetanus-acellular pertussis vaccine) was tested in a repeated dose toxicity study in rabbits. After three intramuscular doses, the only changes observed were those commonly related to a vaccine-elicited inflammatory reaction. Subsequently, the effects of unadjuvanted RSVPreF3 vaccine on female fertility, embryo-fetal, and postnatal development of offspring were evaluated in rats and rabbits. There were no effects on pregnancy, delivery, lactation, or the pre- and postnatal development of offspring. In conclusion, the RSVPreF3 vaccine was well-tolerated locally and systemically and was not associated with any adverse effects on female reproductive function or on the pre- and postnatal growth and development of offspring.
The effects of gait speed on plantar pressure variables in individuals with normal foot posture and flatfoot.

PURPOSE It is not known how gait speed affects plantar pressure characteristics in flatfoot. The aim of this work was to investigate the effects of gait speed on plantar pressure variables in flatfoot by comparing it to normal foot posture. METHODS Thirty individuals with flatfoot and 30 individuals with normal foot posture were recruited. Plantar pressure variables were obtained by a pressure-sensitive mat at self-selected slow, normal, and fast speeds. All assessments were performed on the dominant foot, and three satisfactory steps were obtained for each gait speed condition. The order of gait speeds was randomized. RESULTS In the flatfoot group, the contact area was higher in the midfoot, third metatarsal, and hallux at all speeds, also in the second metatarsal at slow and normal speeds than the normal foot posture group ( p < 0.05). The maximum force was higher in the midfoot and hallux at all speeds in the flatfoot group ( p < 0.05). Also, the maximum force was lower in the first metatarsal at normal and fast speeds, and in the lateral heel at fast speed ( p < 0.05). In the flatfoot group, the peak pressure was found to be higher in the hallux at slow speed, but to be lower in the first metatarsal at fast speed ( p < 0.05). Further, plantar pressure distribution was affected by gait speed in both feet. CONCLUSIONS Analysis of plantar pressure variables should be performed at different gait speeds.
Expression of Endogenous Angiotensin-Converting Enzyme 2 in Human Induced Pluripotent Stem Cell-Derived Retinal Organoids

Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.
Comparing outcomes in chronic depression following inpatient psychotherapy for patients continuing versus discontinuing antidepressant medication.

Research indicates combination of psychotherapy and antidepressant medication (ADM) provide cumulative effects and thus outperforms monotherapy in treating chronic depression. In this quasi-experimental study, we explored symptom change for patients with chronic depression treated with ADM when presenting for a 12-week psychotherapeutic inpatient treatment program. We compared outcomes through treatment and follow-up of patients who continued medication with those who discontinued. We also tested possible moderator effects of initial depression severity on change between the groups. Based on prior research, we hypothesized that combination treatment would yield better results (i.e., more reduction in depression). Patients (N=112) were referred from general practitioners or local secondary health care. Outcome was measured by Beck Depression Inventory-II (BDI-II) and comparisons were carried out using multi-level modelling. While 35 patients discontinued ADM during treatment, 77 continued. Both continuers and discontinuers had a significant treatment effect that was maintained at one-year follow up. There was no difference in outcome between continuers and discontinuers of ADM. Patients with severe depression had significantly more symptom improvement than patients with moderate depression, but depression severity did not affect outcomes across continuers and discontinuers of ADM differently. The results could indicate that patients had developed resistance and/or tolerance to the prophylactic effects of medication and that ADM did not contribute to the reduction of depressive symptoms. The findings may also indicate psychotherapy alone in some instances can be a viable alternative to continued combined treatment. Clinicians should carefully assess benefits of patients´ ongoing use of antidepressant medication when entering psychotherapy.