Miracle-dz/UniFAR-FTUs huggingface dataset:
Repressing expression of difficult‐to‐express recombinant proteins during the selection process increases productivity of CHO stable pools

More than half of licensed therapeutic recombinant proteins (r‐proteins) are manufactured using constitutively‐expressing, stably‐transfected Chinese hamster ovary (CHO) clones. While constitutive CHO expression systems have proven their efficacy for the manufacturing of monoclonal antibodies, many next‐generation therapeutics such as cytokines and bispecific antibodies as well as biological targets such as ectodomains of transmembrane receptors remain intrinsically challenging to produce. Herein, we exploited a cumate‐inducible CHO platform allowing reduced expression of various classes of r‐proteins during selection of stable pools. Following stable pool generation, fed‐batch productions showed that pools generated without cumate (OFF‐pools) were significantly more productive than pools selected in the presence of cumate (ON‐pools) for 8 out of the 10 r‐proteins tested, including cytokines, G‐protein coupled receptors (GPCRs), the HVEM membrane receptor ectodomain, the multifunctional protein High Mobility Group protein B1 (HMGB1), as well as monoclonal and bispecific T‐cell engager antibodies. We showed that OFF‐pools contain a significantly larger proportion of cells producing high levels of r‐proteins and that these cells tend to proliferate faster when expression is turned off, suggesting that r‐protein overexpression imposes a metabolic burden on the cells. Cell viability was lower and pool recovery was delayed during selection of ON‐pools (mimicking constitutive expression), suggesting that high producers were likely lost or overgrown by faster‐growing, low‐producing cells. We also observed a correlation between the expression levels of the GPCRs with Binding immunoglobulin Protein, an endoplasmic reticulum (ER) stress marker. Taken together, these data suggest that using an inducible system to minimize r‐protein expression during stable CHO pool selection reduces cellular stresses, including ER stress and metabolic burden, leading to pools with greater frequency of high‐expressing cells, resulting in improved volumetric productivity.
One electrogram tracing tells all: What is the mechanism of this tachycardia and where is the catheter positioned?

A 33‐year‐old man without any overt structural heart disease was referred to our hospital for catheter ablation of a wide QRS complex tachycardia with right bundle branch block (RBBB) morphology and a superior axis. A 12‐lead electrocardiogram during sinus rhythm revealed no pre‐excitation. During sinus rhythm, the atrio‐His interval and His‐ventricular (HV) intervals were 94 ms and 46 ms, respectively. The induced clinical tachycardia with a cycle length (TCL) of 318 ms and HV interval of −28 ms exhibited ventriculoatrial dissociation. The intracardiac electrograms during and after overdrive pacing from the left ventricle (LV) with a pacing cycle length of 300 ms are shown in Figure 1. What is the diagnosis and mechanism of this tachycardia, and where is the catheter position that corresponds to the tachycardia circuit? Figure 2.
Parents’ lived experience of living with and caring for their burn-injured child in a home setting

ABSTRACT Purpose When a burn injured child is discharged from hospital to its home, the responsibility for the after-care treatment is transferred to the parent(s). A knowledge gap exists concerning how parents experience caring for a burn-injured child at home after discharge. The aim is to gain an in-depth understanding of parents’ lived experience of living with and caring for their burn-injured child in a home setting. Methods Twenty-four parents of burn-injured children treated at a Norwegian burn centre were interviewed 74 to 195 days after the burn accident (June 2017 to November 2018). A phenomenological hermeneutic approach was chosen, using a Ricoeur-inspired textual in-depth analysis method. NVivo 12 Plus and COREQ were used. Results Four themes emerged. The parents’ experienced feelings had been embodied and would stay forever. They felt left alone to continue the medical treatment at home without having the necessary skills. The parents grieved over the lost past and feared the unknown future. They longed to meet or be contacted by staff members who knew them and their life situation. Conclusions Healthcare professionals should see returning home as part of the course of illness and that right support during the hospital can prevent challenges after discharge.
Emotions, fast and slow: processing of emotion words is affected by individual differences in need for affect and narrative absorption

ABSTRACT Emotional words have consistently been shown to be processed differently than neutral words. However, few studies have examined individual variability in emotion word processing with longer, ecologically valid stimuli (beyond isolated words, sentences, or paragraphs). In the current study, we re-analysed eye-tracking data collected during story reading to reveal how individual differences in need for affect and narrative absorption impact the speed of emotion word reading. Word emotionality was indexed by affective-aesthetic potentials (AAP) calculated by a sentiment analysis tool. We found that individuals with higher levels of need for affect and narrative absorption read positive words more slowly. On the other hand, these individual differences did not influence the reading time of more negative words, suggesting that high need for affect and narrative absorption are characterised by a positivity bias only. In general, unlike most previous studies using more isolated emotion word stimuli, we observed a quadratic (U-shaped) effect of word emotionality on reading speed, such that both positive and negative words were processed more slowly than neutral words. Taken together, this study emphasises the importance of taking into account individual differences and task context when studying emotion word processing.
LAST: LAtent Space-Constrained Transformers for Automatic Surgical Phase Recognition and Tool Presence Detection

When developing context-aware systems, automatic surgical phase recognition and tool presence detection are two essential tasks. There exist previous attempts to develop methods for both tasks but majority of the existing methods utilize a frame-level loss function (e.g., cross-entropy) which does not fully leverage the underlying semantic structure of a surgery, leading to sub-optimal results. In this paper, we propose multi-task learning-based, LAtent Space-constrained Transformers, referred as LAST, for automatic surgical phase recognition and tool presence detection. Our design features a two-branch transformer architecture with a novel and generic way to leverage video-level semantic information during network training. This is done by learning a non-linear compact presentation of the underlying semantic structure information of surgical videos through a transformer variational autoencoder (VAE) and by encouraging models to follow the learned statistical distributions. In other words, LAST is of structure-aware and favors predictions that lie on the extracted low dimensional data manifold. Validated on two public datasets of the cholecystectomy surgery, i.e., the Cholec80 dataset and the M2cai16 dataset, our method achieves better results than other state-of-the-art methods. Specifically, on the Cholec80 dataset, our method achieves an average accuracy of 93.12±4.71%, an average precision of 89.25±5.49%, an average recall of 90.10±5.45% and an average Jaccard of 81.11 ±7.62% for phase recognition, and an average mAP of 95.15±3.87% for tool presence detection. Similar superior performance is also observed when LAST is applied to the M2cai16 dataset.
Pharmacological antagonism of receptor for advanced glycation end products signaling promotes thermogenesis, healthful body mass and composition, and metabolism in mice

Optimal body mass and composition as well as metabolic fitness require tightly regulated and interconnected mechanisms across tissues. Disturbances in these regulatory networks tip the balance between metabolic health versus overweight and obesity and their complications. The authors previously demonstrated roles for the receptor for advanced glycation end products (RAGE) in obesity, as global‐ or adipocyte‐specific deletion of Ager (the gene encoding RAGE) protected mice from high‐fat diet‐induced obesity and metabolic dysfunction.
Influencing the Insulin System by Placebo Effects in Patients With Diabetes Type 2 and Healthy Controls: A Randomized Controlled Trial

ABSTRACT Objective The objective of this study was to investigate whether placebo effect induced by pharmacological conditioning with intranasal insulin can affect glucose, insulin, C-peptide, hunger, and memory in patients with diabetes type 2 and healthy controls. Methods Placebo effect was induced by pharmacological conditioning. Thirty-two older patients (mean age = 68.3 years) with diabetes type 2 and age- and sex-matched thirty-two healthy older adults (mean age = 67.8 years) were randomly assigned to a conditioned or a control group. On day 1, conditioned group received six administrations of intranasal insulin with a conditioned stimulus (CS; smell of rosewood oil), whereas the control group received a placebo with the CS. On day 2, both groups received a placebo spray with the CS. Glucose, insulin, and C-peptide were repeatedly measured in blood. Hunger and memory were assessed with validated measures. Results Intranasal insulin stabilized dropping glucose levels in patients (B = 0.03, SE = 0.02, p = .027) and healthy men (B = 0.046, SE = 0.02, p = .021), and decreased C-peptide levels in healthy controls (B = 0.01, SE = 0.001, p = .008). Conditioning also prevented the drop of glucose levels but only in men (both healthy and patients; B = 0.001, SE = 0.0003, p = .024). Conditioning significantly decreased hunger in healthy participants (B = 0.31, SE = 0.09, p < .001). No effects were found on other measures. Conclusions Placebo effect induced by conditioning with intranasal insulin modifies blood glucose levels and decreases hunger in older adults, but its effects depend on health status and sex. Insulin conditioning might be beneficial for groups suffering from intensive hunger but seems not be particularly suitable for blood glucose reduction. Trial Registration Netherlands Trial Register, NL7783 (https://www.trialregister.nl/trial/7783).
Mental Health Client Experiences of Telehealth in Aotearoa New Zealand During the COVID-19 Pandemic: Lessons and Implications

Background The COVID-19 pandemic and consequent lockdowns disrupted mental health service delivery worldwide, accelerating the adoption of telehealth services to provide care continuity. Telehealth-based research largely highlights the value of this service delivery method for a range of mental health conditions. However, only limited research exists exploring client perspectives of mental health services delivered via telehealth during the pandemic. Objective This study aimed to increase understanding of the perspectives of mental health clients around services provided via telehealth over the 2020 COVID-19 lockdown in Aotearoa New Zealand. Methods Interpretive description methodology underpinned this qualitative inquiry. Semistructured interviews were conducted with 21 individuals (15 clients and 7 support people; 1 person was both a client and support person) to explore their experiences of outpatient mental health care delivered via telehealth during the COVID-19 pandemic in Aotearoa New Zealand. A thematic analysis approach supported by field notes was used to analyze interview transcripts. Results The findings reveal that mental health services delivered via telehealth differed from those provided in person and led some participants to feel they need to manage their own care more actively. Participants highlighted several factors affecting their telehealth journey. These included the importance of maintaining and building relationships with clinicians, the creation of safe spaces within client and clinician home environments, and clinician readiness in facilitating care for clients and their support people. Participants noted weaknesses in the ability of clients and clinicians to discern nonverbal cues during telehealth conversations. Participants also emphasized that telehealth was a viable option for service delivery but that the reason for telehealth consultations and the technicalities of service delivery needed to be addressed. Conclusions Successful implementation requires ensuring solid relationship foundations between clients and clinicians. To safeguard minimum standards in delivering telehealth-based care, health professionals must ensure that the intent behind telehealth appointments is clearly articulated and documented for each person. In turn, health systems must ensure that health professionals have access to training and professional guidance to deliver effective telehealth consultations. Future research should aim to identify how therapeutic engagement with mental health services has changed, following a return to usual service delivery processes.
Increasing evidence of human infections by the neurotropic Borna disease virus 1 (BoDV-1)

Due to relatively rare instances of human infections by the Borna disease virus 1 (BoDV-1) and the difficulty of developing and validating a test for diagnosing it, human cases of fatal encephalitis caused by BoDV-1 have been difficult to confirm. Zoonotic transmissions of BoDV-1 have also been suspected but have not been definitively ascertained. Using serum and cerebrospinal fluid of at-risk patients, who were living in northern and eastern parts of Germany, the authors of a recent study1 successfully developed and validated a new workflow for rapid testing of BoDV-1 infections in humans. Using next-generation sequencing method, they were able to recover the full-length BoDV-1 genome from the patient's brain tissue that phylogenetically match the viral sequences to BoDV-1 strains found in shrews and domesticated animals, implicating zoonotic transmissions of this virus. This editorial aims to raise awareness about this emerging neurotropic virus that might have important public health implications.
The Continuum of Severity of Functional Impairment Due to Indoor Air Symptoms

Individuals with indoor air–related symptoms are a heterogeneous group. Those with more functional impairment due to symptoms have more somatic, psychiatric, and functional comorbidities. Multiple health problems may increase the risk for higher functional impairment and prevent individuals from gaining from interventions. This should be better considered in future research and clinical practice. Objective The aim of the study is to study functional impairment due to indoor air–related symptoms and associated characteristics. Methods A questionnaire survey of a random sample of Finnish people aged 25 to 64 years. Analyses were done using multivariate multinomial logistic regression. Results A total of 23.1% reported indoor air–related symptoms, 1.8% severe functional impairment due to symptoms, 5.3% moderate, 11.1% mild, and 4.9% reported no impairment. Those with severe functional impairment showed the strongest associations with comorbid diseases, for example, asthma and irritable bowel syndrome, perceived sensitivities to several environmental factors, like chemicals, and likelihood of having symptoms in multiple organs, while those with no or little functional impairment showed weak or even inverse associations. Similar results emerged with severity of indoor air–related symptoms. Conclusions Individuals with indoor air–related symptoms are a very heterogeneous group. This should be better considered in future research and clinical practice.
Trajectories of depressive symptoms among older African Americans: the influence of neighborhood characteristics and gender

Abstract Objectives Focusing on older African Americans, this study aims to (1) identify 9-year trajectories of depressive symptoms, (2) examine the association between baseline neighborhood characteristics (i.e., social cohesion and physical disadvantage) and trajectories of depressive symptoms, and (3) test whether the effects of neighborhood characteristics on depressive symptoms trajectories differ by gender. Methods Data came from the National Health and Aging Trend Study. Older African Americans at baseline were selected (N = 1662) and followed up for eight rounds. Depressive symptom trajectories were estimated using group-based trajectory modeling. Weighted multinomial logistic regressions were conducted. Results Three trajectories of depressive symptoms were identified: “persistently low,” “moderate and increasing,” and “high and decreasing” (Objective 1). Objective 2 and 3 were partially supported. Specifically, high perceived neighborhood social cohesion was associated with a lower relative risk of being on the “moderate and increasing” versus the “persistently low” trajectory (RRR = 0.64, p < 0.01). The association between neighborhood physical disadvantage and depressive symptom trajectories was stronger among older African American men compared to women. Conclusions High levels of neighborhood social cohesion may protect against increasing depressive symptoms in older African Americans. Compared to women, older African American men may be more vulnerable to negative mental health effects of neighborhood physical disadvantage.
On a stopping time of Starr and its use in estimating the number of transmission sources

Consider N sources, each of which transmits signals according to a renewal process with a common, known, underlying distribution. Sequential point estimators for N, which are asymptotically efficient in comparison to the best fixed stopping strategy, are derived. Confidence statements for N, and applications to the problem of estimating finite populations are discussed. The exact limiting distribution, and moments, of the stopping time we use, which was suggested by Starr, are derived.
Encapsulated papillary carcinoma of the breast: does it have a native basement membrane?

Encapsulated papillary carcinoma (EPC) is surrounded by a thick fibrous capsule‐like structure, which is interpreted as a thickened basement membrane (BM). This study aimed to describe the geometric characteristics of the EPC capsule and to refine whether it is an expansion of the BM or a stromal reactive process.
Low-Molecular-Weight Hyaluronic Acid Contributes to Noise-Induced Cochlear Inflammation

Introduction: Our previous work indicated that the activation of the Toll-like receptor (TLR) 4 signaling pathway contributed to noise-induced cochlear inflammation. Previous studies have reported that low-molecular-weight hyaluronic acid (LMW-HA) accumulates during aseptic trauma and promotes inflammation by activating the TLR4 signaling pathway. We hypothesized that LMW-HA or enzymes synthesizing or degrading HA might be involved in noise-induced cochlear inflammation. Methods: The present study included two arms. The first arm was the noise exposure study, in which TLR4, proinflammatory cytokines, HA, hyaluronic acid synthases (HASs), and hyaluronidases (HYALs) in the cochlea as well as auditory brainstem response (ABR) thresholds were measured before and after noise exposure. The second arm was analysis of HA delivery-induced reactions, in which control solution, high-molecular-weight HA (HMW-HA), or LMW-HA was delivered into the cochlea by cochleostomy or intratympanic injection. Then, the ABR threshold and cochlear inflammation were measured. Results: After noise exposure, the expression of TLR4, proinflammatory cytokines, HAS1, and HAS3 in the cochlea significantly increased over the 3rd to 7th day post-noise exposure (PE3, PE7). The expression of HYAL2 and HYAL3 dramatically decreased immediately after noise exposure, gradually increased thereafter to levels significantly greater than the preexposure level on PE3, and then rapidly returned to the preexposure level on PE7. The expression of HA, HAS2, and HYAL1 in the cochlea remained unchanged after exposure. After cochleostomy or intratympanic injection, both the hearing threshold shifts and the expression of TLR4, TNF-α, and IL-1β in the cochleae of the LMW-HA group were obviously greater than those of the control group and HMW-HA group. The expression of proinflammatory cytokines in the LMW-HA and control groups on the 7th day (D7) after cochleostomy tended to increase compared to that on the 3rd day (D3), whereas levels in the HMW-HA group tended to decrease on D7 compared to D3. Conclusion: HAS1, HAS3, HYAL2, and HYAL3 in the cochlea are involved in acoustic trauma-induced cochlear inflammation through the potential proinflammatory function of LMW-HA.
Feasibility, Acceptability, and Preliminary Effectiveness of Cognitive-Reminiscence Therapy among Jordanian People with Major Depressive Disorders: A Mixed Methods Study

Abstract Depression is a major public health problem around the world. Negative automatic thoughts are cognitive errors that build in the mind, leading to depression. Cognitive-reminiscence therapy is one of the most effective psychosocial methods for managing cognitive errors. This study aimed to evaluate cognitive reminiscence therapy’s feasibility, acceptability, and preliminary effectiveness among Jordanian patients with major depressive disorder. A convergent-parallel design was employed. A convenience sampling method was used to recruit 36 participants (Site 1: n = 16, Site 2: n = 20). A total of 31 participants were included in the analysis, divided into six groups, with 5–6 participants in each group. Cognitive-reminiscence therapy included eight supported sessions of up to 2 h each, delivered over 4 wk. Recruitment, adherence, retention, and attrition rates of 80%, 86.1%, and 13.9%, respectively, indicated the feasibility of the therapy. The acceptability of therapy was reflected in the following four themes: Positive Cognitive Reminiscence Therapy Perspectives and Outcomes; Cognitive Reminiscence Therapy Sessions Challenge; Suggestions for Improving Cognitive Reminiscence Therapy Sessions; and Motivational Home Activities. A significant reduction in the mean of depressive symptoms and negative automatic thoughts and a significant increase in the self-transcendence mean demonstrated the effectiveness of the intervention. The study’s results suggest that cognitive reminiscence therapy is feasible and acceptable among patients with major depressive disorder. This therapy is a promising nursing intervention to reduce depressive symptoms and negative automatic thoughts and increase self-transcendence for those patients.
Reproduced out-of-plane ferroelectricity in monolayer SnTe van der Waals heterostructures

Due to the shrinking in size of nonvolatile memory devices, the two-dimensional ferroelectric van der Waals (vdW) heterostructures have received huge attention. However, it is still difficult to maintain the out-of-plane (OOP) ferroelectricity. In this work, we have theoretically investigated the relationship between the ferroelectricity and the strain of bulk and few-layer SnTe by first-principles calculations. The results indicate that the α-SnTe can exist stably within the strain between −6% and 6%, and the complete OOP polarization occurs within the strain between −4% and −2%. Unfortunately, the OOP polarization disappears while the bulk α-SnTe is thinned to a few layers. However, the complete OOP polarization recurs in monolayer SnTe/PbSe vdW heterostructures, which is due to the strong interface coupling. Our findings provide an effective way to enhance ferroelectric performance, which is beneficial for the design of ultra-thin ferroelectric devices.