Miracle-dz/UniFAR-FTUs huggingface dataset:
How Do Young Women with Cancer Experience Oncofertility Counselling during Cancer Treatment? A Qualitative, Single Centre Study at a Danish Tertiary Hospital

Simple Summary Adolescents and young adults (AYAs) diagnosed with cancer undergo a range of cancer treatments with intension of being cured. It is well-documented that cancer treatment induces a risk of infertility due to ovarian damage. In recent years fertility preservation options for female AYAs with cancer have developed with opportunities for pregnancy after completion of cancer treatment. Despite international guidelines, a high level of evidence underpins the insufficiency of fertility counselling towards this patient group. The aim of this qualitative study was to examine the experience of fertility counselling from the AYAs perspective, and we strive to increase the attention towards the need of improvement and developing national guidelines at international level to ensure adequate and uniform fertility information. Abstract Background: Adolescents and young adults (AYAs) with cancer are at risk of therapy-induced infertility. The importance of initial and specialized fertility counselling to this patient group is undisputed. Despite international guidelines, oncofertility counselling is still inadequate. The purpose of this study was to examine how female AYA cancer patients and survivors experienced initial and specialized oncofertility counselling, and to present their specific suggestions on how to improve the oncofertility counselling. Methods: Twelve individual semi-structured interviews were performed with AYAs aged 20–35 with cancer or who were survivors. Participants were recruited via a youth support centre and social organization for AYAs with cancer. Data was analysed using thematic analysis. Results: Three main themes were found: Support is needed for navigating the fertility information jungle; The doctor’s approach determines the content of the patient consultation; Inadequate and worrying information causes mistrust and frustration. Conclusion: Results indicate a continuing problem regarding insufficient oncofertility counselling to AYAs with cancer. To ensure adequate and uniform information, especially in the initial oncofertility counselling, national guidelines for oncology specialists are suggested including multidisciplinary effort and collaboration between oncology and fertility specialists in mind. In addition, participants suggest focus on communication skills.
Safinamide Improves Non-Motor Symptoms Burden in Parkinson’s Disease: An Open-Label Prospective Study

Some studies observed a benefit of Parkinson’s disease (PD) patients after treatment with safinamide in some non-motor symptoms (NMSs). The aim of this study was to analyze the effectiveness of safinamide on NMS burden in PD. SAFINONMOTOR (an open-label study of the effectiveness of safinamide on non-motor symptoms in Parkinson’s disease patients) is a prospective open-label single-arm study conducted in five centers from Spain. The primary efficacy outcome was the change from baseline (V1) to the end of the observational period (6 months) (V4) in the non-motor symptoms scale (NMSS) total score. Between May/2019 and February/2020 50 patients were included (age 68.5 ± 9.12 years; 58% females; 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The NMSS total score was reduced by 38.5% (from 97.5 ± 43.7 in V1 to 59.9 ± 35.5 in V4; p < 0.0001). By domains, improvement was observed in sleep/fatigue (−35.8%; p = 0.002), mood/apathy (−57.9%; p < 0.0001), attention/memory (−23.9%; p = 0.026), gastrointestinal symptoms (−33%; p = 0.010), urinary symptoms (−28.3%; p = 0.003), and pain/miscellaneous (−43%; p < 0.0001). Quality of life (QoL) also improved with a 29.4% reduction in the PDQ-39SI (from 30.1 ± 17.6 in V1 to 21.2 ± 13.5 in V4; p < 0.0001). A total of 21 adverse events in 16 patients (32%) were reported, 5 of which were severe (not related to safinamide). Dyskinesias and nausea were the most frequent (6%). Safinamide is well tolerated and improves NMS burden and QoL in PD patients with severe or very severe NMS burden at 6 months.
Potency-Enhancing Mutations of Gating Modifier Toxins for the Voltage-Gated Sodium Channel NaV1.7 Can Be Predicted Using Accurate Free-Energy Calculations

Gating modifier toxins (GMTs) isolated from venomous organisms such as Protoxin-II (ProTx-II) and Huwentoxin-IV (HwTx-IV) that inhibit the voltage-gated sodium channel NaV1.7 by binding to its voltage-sensing domain II (VSDII) have been extensively investigated as non-opioid analgesics. However, reliably predicting how a mutation to a GMT will affect its potency for NaV1.7 has been challenging. Here, we hypothesize that structure-based computational methods can be used to predict such changes. We employ free-energy perturbation (FEP), a physics-based simulation method for predicting the relative binding free energy (RBFE) between molecules, and the cryo electron microscopy (cryo-EM) structures of ProTx-II and HwTx-IV bound to VSDII of NaV1.7 to re-predict the relative potencies of forty-seven point mutants of these GMTs for NaV1.7. First, FEP predicted these relative potencies with an overall root mean square error (RMSE) of 1.0 ± 0.1 kcal/mol and an R2 value of 0.66, equivalent to experimental uncertainty and an improvement over the widely used molecular-mechanics/generalized born-surface area (MM-GB/SA) RBFE method that had an RMSE of 3.9 ± 0.8 kcal/mol. Second, inclusion of an explicit membrane model was needed for the GMTs to maintain stable binding poses during the FEP simulations. Third, MM-GB/SA and FEP were used to identify fifteen non-standard tryptophan mutants at ProTx-II[W24] predicted in silico to have a at least a 1 kcal/mol gain in potency. These predicted potency gains are likely due to the displacement of high-energy waters as identified by the WaterMap algorithm for calculating the positions and thermodynamic properties of water molecules in protein binding sites. Our results expand the domain of applicability of FEP and set the stage for its prospective use in biologics drug discovery programs involving GMTs and NaV1.7.
Variation of Autonomic Nervous System Function by Age and Gender in Thai Ischemic Stroke Patients

Background: Ischemic stroke is one of the major causes of disability and mortality. Its effects on the autonomic nervous system (ANS) through nonlinear heart rate variability (HRV) and pulse transit time (PTT) have not been well explored among Thai patients. Objective: This study aims to demonstrate the association between ANS and ischemic stroke through nonlinear HRV and PTT. Methods: In total, 111 patients were enrolled in the study and their short-term HRV and PTT data were collected. Results: Parasympathetic tone was higher in elderly patients (≥60 years). The elderly patients had a higher SD1 but lower SD2 and SD2/SD1 than the younger patients, and a similar pattern was found in the female patients compared to the male patients. These findings were supported by the results of the Poincaré plots. Older and female patients had circular plots and approximately round plots, respectively. Moreover, the parasympathetic nervous system (PNS) response was moderate and positively associated with SD1 (r = 0.47, p < 0.001) and PTT (r = 0.29, p = 0.002), and negatively associated with SD2 and SD2/SD1 (r = −0.47, p < 0.001), after controlling for age and sex. Conclusions: The PNS response was predominant in older and female patients whereas the sympathetic response was lower than in the younger and male patients, which reflected certain characteristics of ANS response to ischemic stroke. Moreover, nonlinear parameters of SD1, SD2, SD2/SD1, and Poincaré plots including PTT are useful and recommended in investigating ANS, particularly in PNS, among ischemic stroke patients.
Effect of Freshly Isolated Bone Marrow Mononuclear Cells and Cultured Bone Marrow Stromal Cells in Graft Cell Repopulation and Tendon-Bone Healing after Allograft Anterior Cruciate Ligament Reconstruction

Graft cell repopulation and tendon-bone tunnel healing are important after allograft anterior cruciate ligament reconstruction (ACLR). Freshly isolated bone marrow mononuclear cells (BMMNCs) have the advantage of short isolation time during surgery and may enhance tissue regeneration. Thus, we hypothesized that the effect of intra-articular BMMNCs in post-allograft ACLR treatment is comparable to that of cultured bone marrow stromal cells (BMSCs). A rabbit model of hamstring allograft ACLR was used in this study. Animals were randomly assigned to the BMMNC, BMSC, and control groups. Fresh BMMNCs isolated from the iliac crest during surgery and cultured BMSCs at passage four were used in this study. A total of 1 × 107 BMMNCs or BMSCs in 100 µL phosphate-buffered saline were injected into the knee joint immediately after ACLR. The control group was not injected with cells. At two and six weeks post operation, we assessed graft cell repopulation with histological and cell tracking staining (PKH26), and tendon-bone healing with histological micro-computed tomography and immunohistochemical analyses for collagen I and monocyte chemoattractant protein-1 (MCP1). At two weeks post operation, there was no significant difference in the total cell population within the allograft among the three groups. However, the control group showed significantly higher cell population within the allograft than that of BM cell groups at six weeks. Histological examination of proximal tibia revealed that the intra-articular delivered cells infiltrated into the tendon-bone interface. Compared to the control group, the BM cell groups showed broader gaps with interfacial fibrocartilage healing, similar collagen I level, and higher MCP1 expression in the early stage. Micro-CT did not reveal any significant difference among the three groups. BMMNCs and BMSCs had comparable effects on cell repopulation and interfacial allograft-bone healing. Intra-articular BM cells delivery had limited benefits on graft cell repopulation and caused higher inflammation than that in the control group in the early stage, with fibrocartilage formation in the tendon-bone interface after allograft ACLR.
Socialization in Commercial Breeding Kennels: The Use of Novel Stimuli to Measure Social and Non-Social Fear in Dogs

Simple Summary Owner-based reports of dogs presumed to come from commercial breeding kennels (CBKs) suggest high levels of fear in this population. Fear in kenneled dogs is a serious behavioral welfare concern as it may lead to both acute and chronic stress. Novel social and non-social stimuli have been shown to elicit behaviors associated with fear in animals. New knowledge on the levels of fear in dogs from CBKs could be used to further refine protocols intended for assessment of welfare in CBKs and to improve breeders’ management practices. The aim of this study, therefore, was to evaluate how dogs from CBKs reacted to social (i.e., a person approaching) and non-social (i.e., a traffic cone and a dog statue) stimuli, and to perform a preliminary evaluation of how these responses might be used as indicators of dogs’ overall socialization levels in kennels. Results revealed that dogs had primarily mildly fearful responses to the stimuli presented. These findings are encouraging as extreme fearful reactions were rarely recorded. Nevertheless, there is a clear margin for commercial breeders to improve the socialization protocols in their kennels to better incorporate both social and non-social stimuli. Abstract Understanding the behavioral welfare of dogs in commercial breeding kennels (CBKs) is important for improving breeders’ management practices as well as dog welfare. In the current study, breeding dogs from CBKs were exposed to novel stimuli to evaluate their behavioral responses, with emphasis on indicators of fear. Subjects were presented with a standard stranger-approach test, a traffic cone, and a realistic dog statue. Sixty dogs were exposed to the three stimuli and behavioral responses were scored using an ethogram developed for this study. Dogs spent significantly more time investigating the environment, staying further away from the stimulus, and they took longer to approach and investigate when presented with the cone than with the dog statue or stranger (p < 0.01). These findings suggest that the cone elicited more fear-related behaviors than the dog statue and stranger. Given these results, in addition to socializing their dogs to unfamiliar people and other dogs within their kennels, commercial breeders should be encouraged to increase the exposure of their dogs to more diverse novel stimuli to reduce non-social fear and support the welfare of dogs while they reside in the kennel and when they transition to new homes.
Gender Differences in Complete Blood Count and Inflammatory Ratios among Patients with Bipolar Disorder

Background: Evidence suggested that inflammation may be involved in the etiopathogenesis of bipolar disorder (BD), a chronic psychiatric condition affecting around 2–3% of the general population. However, little is known regarding potential gender differences in peripheral biomarkers of BD, such as neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and monocyte-to-lymphocyte (MLR) ratios. Methods: In total, 197 females and 174 males with BD in different phases (i.e., (hypo)mania, depression, euthymia) were recruited. A blood sample was drawn to perform a complete blood count (CBC). NLR, PLR, and MLR were subsequently calculated, and differences were computed according to the illness phase and gender. Results: PLR was consistently higher in (hypo)manic than depressed patients, in both males and females. No significant gender differences in PLR value were found when considering only (hypo)mania. Conversely, NLR was increased in (hypo)mania only among males, and gender differences were retrieved in the (hypo)manic subgroup. The findings related to MLR were only marginally significant. Higher platelets values were associated with (hypo)mania only in the female group. Basophils and eosinophils appeared gender- but not state-dependent. Conclusions: Our findings provide further evidence that increased PLR levels may be associated with (hypo)mania in bipolar patients, regardless of gender. Moreover, the usefulness of NLR as a peripheral biomarker of BD appeared limited to males while the role of platelets to females. As CBC represents a low-cost and easily accessible test, researchers should investigate in-depth its potential usefulness as a biomarker of BD and other psychiatric disorders.
Dysbiosis and Enhanced Beta-Defensin Production in Hair Follicles of Patients with Lichen Planopilaris and Frontal Fibrosing Alopecia

Despite their distinct clinical manifestation, frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) display similar histopathologic features. Aberrant innate immune responses to endogenous or exogenous triggers have been discussed as factors that could drive inflammatory cascades and the collapse of the stem cell niche. In this exploratory study, we investigate the bacterial composition of scalp skin and plucked hair follicles (HF) of patients with FFA, LPP and alopecia areata circumscripta (AAc), as well as healthy individuals, in relation to cellular infiltrates and the expression of defense mediators. The most abundant genus in lesional and non-lesional HFs of LPP and FFA patients was Staphylococcus, while Lawsonella dominated in healthy individuals and in AAc patients. We observed statistically significant differences in the ratio of Firmicutes to Actinobacteria between healthy scalp, lesional, and non-lesional sites of FFA and LPP patients. This marked dysbiosis in FFA and LPP in compartments close to the bulge was associated with increased HβD1 and HβD2 expression along the HFs from lesional sites, while IL-17A was increased in lesional HF from AAc patients. The data encourage further studies on how exogenous factors and molecular interactions across the HF epithelium could contribute to disease onset and propagation.
Genome Sequence Analysis of First Ross River Virus Isolate from Papua New Guinea Indicates Long-Term, Local Evolution

Ross River virus (RRV) is the most medically significant mosquito-borne virus of Australia, in terms of human morbidity. RRV cases, characterised by febrile illness and potentially persistent arthralgia, have been reported from all Australian states and territories. RRV was the cause of a large-scale epidemic of multiple Pacific Island countries and territories (PICTs) from 1979 to 1980, involving at least 50,000 cases. Historical evidence of RRV seropositivity beyond Australia, in populations of Papua New Guinea (PNG), Indonesia and the Solomon Islands, has been documented. We describe the genomic characterisation and timescale analysis of the first isolate of RRV to be sampled from PNG to date. Our analysis indicates that RRV has evolved locally within PNG, independent of Australian lineages, over an approximate 40 year period. The mean time to most recent common ancestor (tMRCA) of the unique PNG clade coincides with the initiation of the PICTs epidemic in mid-1979. This may indicate that an ancestral variant of the PNG clade was seeded into the region during the epidemic, a period of high RRV transmission. Further epidemiological and molecular-based surveillance is required in PNG to better understand the molecular epidemiology of RRV in the general Australasian region.
The Impact of Physical Education Based on the Adventure Education Programme on Self-Esteem and Social Competences of Adolescent Boys

The objective of this study is to analyse the impact of physical education based on the adventure education programme on the social competences of adolescent boys. The participants (n = 70) were 1st grade high school students between 15 and 16 years old. Adolescents’ social competences were measured using the Rosenberg’s Self-Esteem Scale (RSES) and Social Competence Questionnaire (SCQ) before and after the intervention. An experimental repeated-measures design was used, with a comparison group. ANOVA (2 × 2) for interaction group x time showed statistical significance in competences revealed in situations of social exposure (F1, 68 = 5.16, p < 0.05, partial η2 = 0.07) and competences revealed in situations requiring assertiveness (F1, 68 = 4.73, p < 0.05, partial η2 = 0.07). Using the adventure education (AE) programme may be recommended as a way of developing social skill competences revealed in situations of social exposure and competences revealed in situations requiring the assertiveness of adolescents through physical activity that can be easily integrated into the school environment.
Performance of the Transport Layer Security Handshake Over 6TiSCH

This paper presents a thorough comparison of the Transport Layer Security (TLS) v1.2 and Datagram TLS (DTLS) v1.2 handshake in 6TiSCH networks. TLS and DTLS play a crucial role in protecting daily Internet traffic, while 6TiSCH is a major low-power link layer technology for the IoT. In recent years, DTLS has been the de-facto security protocol to protect IoT application traffic, mainly because it runs over lightweight, unreliable transport protocols, i.e., UDP. However, unlike the DTLS record layer, the handshake requires reliable message delivery. It, therefore, incorporates sequence numbers, a retransmission timer, and a fragmentation algorithm. Our goal is to study how well these mechanisms perform, in the constrained setting of 6TiSCH, compared to TCP’s reliability algorithms, relied upon by TLS. We port the mbedTLS library to OpenWSN, a 6TiSCH reference implementation, and deploy the code on the state-of-the-art OpenMote platform. We show that, when the peers use an ideal channel, the DTLS handshake uses up to 800 less and completes 0.6 s faster. Nonetheless, using an unreliable communication link, the DTLS handshake duration suffers a performance penalty of roughly 45%, while TLS’ handshake duration degrades by merely 15%. Similarly, the number of exchanged bytes doubles for DTLS while for TLS the increase is limited to 15%. The results indicate that IoT product developers should account for network characteristics when selecting a security protocol. Neglecting to do so can negatively impact the battery lifetime of the entire constrained network.
Outcome of Different Sequencing and Assembly Approaches on the Detection of Plasmids and Localization of Antimicrobial Resistance Genes in Commensal Escherichia coli

Antimicrobial resistance (AMR) is a major threat to public health worldwide. Currently, AMR typing changes from phenotypic testing to whole-genome sequence (WGS)-based detection of resistance determinants for a better understanding of the isolate diversity and elements involved in gene transmission (e.g., plasmids, bacteriophages, transposons). However, the use of WGS data in monitoring purposes requires suitable techniques, standardized parameters and approved guidelines for reliable AMR gene detection and prediction of their association with mobile genetic elements (plasmids). In this study, different sequencing and assembly strategies were tested for their suitability in AMR monitoring in Escherichia coli in the routines of the German National Reference Laboratory for Antimicrobial Resistances. To assess the outcomes of the different approaches, results from in silico predictions were compared with conventional phenotypic- and genotypic-typing data. With the focus on (fluoro)quinolone-resistant E. coli, five qnrS-positive isolates with multiple extrachromosomal elements were subjected to WGS with NextSeq (Illumina), PacBio (Pacific BioSciences) and ONT (Oxford Nanopore) for in depth characterization of the qnrS1-carrying plasmids. Raw reads from short- and long-read sequencing were assembled individually by Unicycler or Flye or a combination of both (hybrid assembly). The generated contigs were subjected to bioinformatics analysis. Based on the generated data, assembly of long-read sequences are error prone and can yield in a loss of small plasmid genomes. In contrast, short-read sequencing was shown to be insufficient for the prediction of a linkage of AMR genes (e.g., qnrS1) to specific plasmid sequences. Furthermore, short-read sequencing failed to detect certain duplications and was unsuitable for genome finishing. Overall, the hybrid assembly led to the most comprehensive typing results, especially in predicting associations of AMR genes and mobile genetic elements. Thus, the use of different sequencing technologies and hybrid assemblies currently represents the best approach for reliable AMR typing and risk assessment.
Mechanism Integrated Information

The Integrated Information Theory (IIT) of consciousness starts from essential phenomenological properties, which are then translated into postulates that any physical system must satisfy in order to specify the physical substrate of consciousness. We recently introduced an information measure (Barbosa et al., 2020) that captures three postulates of IIT—existence, intrinsicality and information—and is unique. Here we show that the new measure also satisfies the remaining postulates of IIT—integration and exclusion—and create the framework that identifies maximally irreducible mechanisms. These mechanisms can then form maximally irreducible systems, which in turn will specify the physical substrate of conscious experience.