Miracle-dz/UniFAR-FTUs huggingface dataset:
A review of recent advances in the treatment of adults with complicated urinary tract infection

ABSTRACT Introduction Complicated urinary tract infections (cUTIs) entail diverse clinical conditions that could be managed differently and not necessarily with premature empiric therapy. Since multidrug-resistant organisms (MDROs) are widely spreading worldwide, the possibility of encountering these resistant bacteria is inevitably part of the daily life of physicians who manage cUTIs. Areas covered The advances in the management of cUTIs are explored, illustrating: 1) a proposed therapeutical approach to cUTIs within the antimicrobial stewardship context; 2) evidence regarding novel antibiotics targeting MDROs. Evidence research has been performed through MEDLINE/PubMed using appropriate keywords and terms regarding cUTIs published before June 2022. Expert opinion Novel antimicrobial drugs are available in the clinicians’ armamentarium. Selecting the optimal therapy for suitable patients may be challenging given the multifaceted group of cUTIs. Carbapenems use is widely increasing, the role of old β-lactam/β-lactamase inhibitors is constantly revised, and novel drugs lack real-life studies. Understanding the different ranges of the complexity of patients affected by cUTIs may help select the most suitable antibiotic for every single case. More multicentric observational studies targeting cUTIs are needed to elucidate the appropriate drug based on patient characteristics and presentations, providing stronger recommendations for cases encountered in everyday clinical practice.
A systematic literature review of randomized controlled trials evaluating prognosis following treatment for adults with chronic fatigue syndrome

Abstract This systematic review investigated randomized controlled trials evaluating cognitive behavioral therapy (CBT) and graded exercise therapy (GET) for adults with chronic fatigue syndrome (CFS). The objective was to determine prognosis following treatment. Studies were eligible if they were peer-reviewed and investigated treatment at least 12 weeks in duration. Studies were excluded if they used co-morbid diagnoses as entry criteria or if they did not measure fatigue, disability, or functioning. Literature published between 1988 and 2021 was searched using MEDLINE, EMBASE, PsycINFO, and Web of Science. Study quality was assessed using the Effective Public Health Practice Project assessment tool. Outcomes were synthesized when three or more studies reported outcomes obtained from the same validated measurement tool. The review included 15 publications comprising 1990 participants. Following CBT, and at short-term to medium-term follow-up, 44% considered themselves better and 11% considered themselves worse. Following GET, and at post-treatment to short-term follow-up, 43% considered themselves better and 14% considered themselves worse. These outcomes were 8–26% more favorable compared to control conditions. Two-thirds of studies were of moderate quality and the remainder were of weak quality. Limitations of this review relate to the clinical heterogeneity of studies and that most outcomes were self-reported. Results suggest some support for the positive effects of CBT and GET at short-term to medium-term follow-up although this requires further investigation given the inconsistent findings of previous reviews. Findings may not be generalizable to severe CFS. This review was registered with PROSPERO (CRD42018086002).
Persistence and disengagement in failing goals: commentary on Boddez, Van Dessel, & De Houwer

ABSTRACT Boddez, Van Dessel, and De Houwer in their paper “Learned helplessness and its relevance for psychological suffering: A new perspective illustrated with attachment problems, burn-out, and fatigue complaints” advance the idea that failing to reach a goal of personal importance unleashes detrimental processes (i.e. learned helplessness) which spill over to other (similar) goals, in the long run resulting in passivity and psychological suffering. As the authors conceptualise learned helplessness in motivational terms (lack of reinforcement, dysregulation of goal-directed response) and attach great weight to the concept of goal failure, I will comment on three issues inherent in their line of argument from a motivational perspective, that is, from the perspective of persistence and disengagement in personal goals. More specifically, first, I will address the distinction between motivational and functional helplessness, then elaborate on goal-related failure and its consequences, and finally cover the issue of generalising failure experience due to the similarity of goals.
Generalized pustular psoriasis is a disease distinct from psoriasis vulgaris: evidence and expert opinion

ABSTRACT Introduction Generalized pustular psoriasis (GPP) is a rare, severe, clinically heterogeneous disease characterized by flares of widespread, noninfectious, macroscopically visible pustules that occur with or without systemic inflammation, and are associated with significant morbidity and mortality. Historically, GPP has been classified as a variant of psoriasis vulgaris (PV, or plaque psoriasis); however, accumulating evidence indicates that these are distinct conditions, requiring different treatment approaches. Areas covered In this perspective article we review evidence that supports the classification of GPP as distinct from PV. Expert opinion The histopathologic and clinical appearance of GPP is distinct from that of PV and fundamental differences exist between the two conditions in terms of genetic causes and expression-related mechanisms of disease development. GPP results from dysregulation of the innate immune system, with disruption of the interleukin (IL)-36 inflammatory pathway, induction of inflammatory keratinocyte responses, and recruitment of neutrophils. PV is driven by the adaptive immune system, with a key role played by IL-17. Considering GPP as a separate disease will enable greater focus on its specific pathogenesis and the needs of patients. Many treatments for PV have insufficient efficacy in GPP and a therapeutic approach developed specifically for GPP might lead to better patient outcomes. Plain Language Summary Generalized pustular psoriasis (GPP) is a rare disease. During episodes of worsening disease, the immune system attacks the skin. This causes large areas of skin to become red and painful, pus-filled blisters suddenly form. Some people with GPP have a history of another, more common, skin condition called psoriasis vulgaris (PV). People with PV develop patches of scaly, itchy skin. In the past, GPP was classed as a type of PV and treated with the same medicines. However, these medicines do not work well in GPP. Researchers now understand more about what causes GPP and how it differs from PV. GPP can cause medical problems throughout the body, leading to life-threatening complications. This means that people with GPP often need urgent medical treatment in hospitals. People with PV are mostly treated outside of hospitals. Any other medical problems are not usually due to PV itself. Researchers have found several genes that are altered in people with GPP and PV, and they differ between the two diseases. For example, changes in a gene called IL36RN are common in GPP but are not seen in PV. The skin of people with these two diseases also looks different under a microscope. Knowing more about GPP and how it differs from PV will help people with GPP to be diagnosed more quickly. It will also help researchers to develop new medicines specifically for GPP, so people can receive better treatment in the future. Graphical Abtract
The association between baseline circulating progenitor cells and vascular function: The role of aging and risk factors

Background: To investigate the cross-sectional and longitudinal relationships between vascular function and circulating progenitor cell (CPC) counts with respect to aging and exposure to risk factors. Methods: In 797 adult participants, CPCs were enumerated by flow cytometry as CD45med mononuclear cells expressing CD34 epitope and its subsets co-expressing CD133, and chemokine C-X-C motif receptor 4 (CXCR4+). Arterial stiffness was evaluated by tonometry-derived pulse wave velocity (PWV) and microvascular function was assessed as digital reactive hyperemia index (RHI). Results: In cross-sectional analyses, for every doubling in CD34+ cell counts, PWV was 15% higher and RHI was 9% lower, after adjusting for baseline characteristics and risk factors (p for all < 0.01). There were significant CPC-by-age-by-risk factor interactions (p <0.05) for both vascular measures. Among younger subjects (< 48 years), CPC counts were higher in those with risk factors and vascular function was better in those with higher compared to those with lower CPC counts (p for all < 0.0l). In contrast, in older participants, CPCs were not higher in those with risk factors, and vascular function was worse compared to the younger age group. A lower CPC count at baseline was an independent predictor of worsening vascular function during 2-year follow-up. Conclusion: A higher CPC count in the presence of risk factors is associated with better vascular function among younger individuals. There is no increase in CPC count with risk factors in older individuals who have worse vascular function. Moreover, a higher CPC count is associated with less vascular dysfunction with aging.
Comparative Studies on Local Barrier Field Variations Above Field-Adsorbed Helium and Neon with a Micro-Probe Hole Field Ion Microscope

Abstract The local field ion emission properties of helium and neon around a step edge atom of W(112) were examined at liquid nitrogen temperature using a micro-probe hole field ion microscope combined with a pulse-counting analysis. We have analyzed the mapped field ion densities obtained for both imaging gas atoms at their respective best local image voltages based on the formula for tunneling barrier strength and have evaluated the dipole moment of polarized adatom as well as the local field enhancement factor at the adatom site. We found that the dipole moments of helium and neon adatoms showed the same value, although the best local image field acting on the helium adatom is much higher than that on the neon adatom. We also found the same magnitude of local field enhancement factors for both noble gas field adsorptions. These results imply that the key to the best local image condition is the tunneling barrier field variations above the adatom. The vital role of the imaging gas atoms is to form an optimum dipole moment to create an ideal electric field distribution for the best local image appearance at each atom site depending on the different chemical nature of adatom species.
Vasculogenic gene therapy: No role for revitalization of structural bone allografts

Segmental bone defects are often performed with cryopreserved allografts. They provide immediate stability, but risk nonunion, infection and late stress fracture. Improving the rate and extent of bone revitalization may improve results. Angiogenesis from surgically placed arteriovenous (AV) bundles improves bone blood flow and vitality in cryopreserved rat femora, augmented by vasculogenic growth factors. This study tests the same principal in Yucatan mini‐pigs with a tibial diaphyseal defect, combining surgical angiogenesis with angiogenic gene therapy within cryopreserved orthotopically‐placed allografts. Tibial diaphyseal defects were reconstructed with cryopreserved allografts and rigid internal fixation in 16 mini pigs. Half of the cranial tibial AV bundles placed within the allograft medullary canal were transfected with an adeno‐associated virus containing vascular endothelial growth factor (VEGF) and platelet‐derived growth factor (PDGF) genes (AAV9.VEGF.PDGF). Bone remodeling, angiogenesis, and allograft healing were assessed. During the postoperative survival period 5 of 8 transfected animals developed cutaneous benign vascular lesions at sites remote from the operated hindlimb, causing excessive bleeding. Within the allograft, both medullary (p = 0.013) and cortical (p = 0.009) vascular volumes were higher and vessels more mature than nontransfected allografts. Bone turnover (p = 0.013), bone mineralization (p = 0.018), bone healing (p = 0.008) and graft incorporation (p = 0.006) were all significantly higher in the gene therapy group. In a large animal tibial defect model, gene therapy of implanted AV bundles improved revascularization, remodeling and healing of cryopreserved allografts used for limb reconstruction. However, benign vascular lesions causing excessive bleeding developed in 5 out of 8 pigs transfected with AAV containing genes for VEGF and PDGF. This unforeseen complication makes vasculogenic gene therapy unacceptable for clinical use.
Orofacial pain and dysfunction in patients with Parkinson's disease: A scoping review

Parkinson's disease (PD) is commonly known as a disorder that affects the smooth performance of body movements. In addition to the motor impairments, patients with PD often experience pain. Both motor impairments and pain can occur throughout the body, hence including the orofacial region. However, currently, there is a lack of knowledge on the orofacial manifestations. Since orofacial pain and dysfunction can, amongst others, reduce the quality of life of patients with PD, it is important to explore the prevalence of these symptoms in the PD population.
Experiences of Interpersonal Trauma Among Parents With Intellectual Disabilities: A Systematic Review

Research has suggested highly elevated levels of interpersonal trauma (IPT) among parents with intellectual disabilities (ID), and that such experiences may contribute to the caregiving and child developmental problems often seen in this population. Conflicting results have however been reported, and there is no systematic review on this matter. This study therefore systematically reviewed the empirical evidence concerning (a) prevalence of IPT among parents with ID, and links with (b) caregiving-relevant and (c) child developmental outcomes, in accordance with the PRISMA 2020 guidelines. Searches were conducted in MEDLINE, CINAHL, PsycINFO, and PTSDpubs. Peer-reviewed empirical articles reporting exposure to any form of systematically assessed IPT (unspecified IPT, physical, sexual, and emotional abuse, neglect, prolonged childhood separations from caregivers, witnessing abuse in the family) among parents with ID were included, yielding a final selection of 20 studies. Findings consistently indicated markedly elevated levels of IPT among parents with ID, with a majority (>50%) having experienced some form of IPT. Estimates for both unspecified and specific forms were typically higher than corresponding estimates in other groups at elevated risk, and than meta-analytical general population estimates in comparable countries. Findings regarding caregiving-relevant outcomes were mixed but indicated links with adverse outcomes, particularly regarding parental mental health. Reports pertaining to child developmental outcomes were scant and inconsistent. We highlight important limitations in the extant literature and provide directions for future research and clinical practice.
Limonene protects human skin keratinocytes against UVB‐induced photodamage and photoaging by activating the Nrf2‐dependent antioxidant defense system

Long term exposure to solar ultraviolet B (UVB) radiation is one of the primary factors of premature skin aging and is referred to as photoaging. Also, mammalian skin exposed to UVB triggers an increase in production of α‐melanocyte‐stimulating hormone (α‐MSH), which is critically involved in the pathogenesis of hyperpigmentary skin diseases. This study investigated the protective effect of limonene on UVB‐induced photodamage and photoaging in immortalized human skin keratinocytes (HaCaT) in vitro. Initially, we determined cell viability and levels of reactive oxygen species (ROS) in UVB‐irradiated HaCaT cells. Pretreatment with limonene increased cell viability followed by inhibition of intracellular ROS generation in UVB‐irradiated HaCaT cells. Interestingly, the antioxidative activity of limonene was directly correlated with an increase in expression of endogenous antioxidants, including heme oxygenase 1 (HO‐1), NAD(P)H:quinone oxidoreductase 1 (NQO‐1), and γ‐glutamylcysteine synthetase (γ‐GCLC), which was associated with enhanced nuclear translocation and activation of NF‐E2‐related factor‐2 (Nrf2). Indeed, Nrf2 knockdown reduced limonene's protective effects. Additionally, we observed that limonene treatment inhibited UVB‐induced α‐MSH secretion followed by inhibition of proopiomelanocortin (POMC) via suppression of p53 transcriptional activation. Moreover, limonene prevented UVB‐mediated depletion of tight junction regulatory proteins, including occludin and zonula occludens‐1. On the other hand, limonene treatment significantly decreased matrix metalloproteinase‐2 levels in UVB‐irradiated HaCaT cells. Based on these results, limonene may have a dermato‐protective effect in skin cells by activating the Nrf2‐dependent cellular antioxidant defense system.
In search of a cut‐off apnea–hypopnea index in type 3 home portable monitors to diagnose and treat obstructive sleep apnea: a mathematical simulation

The American Academy of Sleep Medicine (AASM) uses similar apnea–hypopnea index (AHI) cut‐off values to diagnose and define severity of sleep apnea independent of the technique used: in‐hospital polysomnography (PSG) or type 3 portable monitoring (PM). Taking into account that PM theoretically might underestimate the AHI, we explored whether a lower cut‐off would be more appropriate. We performed mathematical re‐calculations on the diagnostic PSG‐AHI (scored using AASM 1999 rules) of 865 consecutive patients with an AHI of ≥20 events/h who started continuous positive airway pressure (CPAP). For a PSG‐AHI of ≥15 events/h re‐scored using AASM 2012 rules (PSG‐AHIAASM2012), a PM‐respiratory event index (REI)AASM2012 cut‐off point of ≥15 events/h resulted in a post‐test probability of 100% of having the disease, but with negative tests in 57.1%. A PM‐REIAASM2012 cut‐off of 8 events/h, still resulted in a positive post‐test probability of 100% but with negative tests in only 34.3%. Combination of the cut‐off values with clinical estimation of being ‘at high risk’ based on Epworth Sleepiness Scale (ESS) and Berlin Questionnaire scores only resulted in a small reduction in the percentage of negative tests (respectively 52.7% and 32.7%). After 6 months, CPAP adherence was not lower using the PM‐REIAASM 2012 cut‐off ≥8 events/h in comparison to ≥15 events/h (median 5.7 vs. 5.8 h/night, p = 0.368) and the reduction in ESS was similar too (median –4 and –5 points, p = 0.083). Consequently, using a lower PM‐REIAASM2012 cut‐off could result in cost savings because of less negative studies and lesser need for a confirmatory PSG or a performance of a CPAP trial.
A neuropsychologically based employment intervention for women with multiple sclerosis: A quasi-randomized controlled trial

Abstract Objective: Job loss is common in multiple sclerosis (MS) and frequently associated with depression, fatigue, and cognitive dysfunction. Identifying these modifiable risk factors and providing “at-risk” women with a neuropsychologically-based intervention may improve employment outcomes. Our study seeks to investigate the utility of a neuropsychologically-based intervention with varying levels of treatment and follow-up, and evaluate treatment and employment outcomes among groups. Method: In this longitudinal, quasi-randomized controlled trial, employed women with MS meeting criteria on screening measures were considered “at-risk” for job instability and randomized to one of two neuropsychological testing interventions (standard-care group received testing and phone feedback of results and recommendations; experimental group received testing and in-person feedback with subsequent care-coordinator calls from a nurse to help coordinate recommendation completion). Participants who did not meet criteria were considered “low-risk” and only followed over time. Results: 56 women in the treatment groups (standard-care = 23; experimental = 33) and 63 women in the follow-only group were analyzed at 1 year. Rates of decreased employment were similar between standard-care (17.4%) and experimental (21.2%) groups (OR = .782, 95% CI .200–3.057). However, the experimental group completed significantly more treatment recommendations, t(53) = −3.237, p = . 002. Rates of decreased employment were also similar between the “low-risk” (17.5%) and “at-risk” groups (19.6%), (OR = .721, 95% CI .285–1.826). Conclusion: Employment outcomes were similar at 1 year between treatment groups receiving differing levels of a neuropsychologically-based intervention, however treatment adherence significantly improved in the experimental group. Treatment groups also had similar employment outcomes as compared to a “low-risk,” no intervention group, suggesting that engaging in either neuropsychological intervention may have impacted job stability.
Self-harm and suicidal ideation in Pakistani youth amid COVID-19 pandemic: findings of a large, cross-sectional study

ABSTRACT Suicide is the fourth leading cause of death among young people. COVID-19 pandemic has exacerbated various factors which could lead to suicidal ideation. Therefore, this study was aimed to assess self-harm and suicidal ideation among university students in Pakistan. We conducted an online, cross-sectional study among students of four major Pakistani universities. The generalized anxiety scale and patient health questionnaire were used to screen students for anxiety, depression and suicidal ideation/self-harm. Suicidal ideation/self-harm was determined from the ninth-item (score ≥1) of the patient health questionnaire. Brief-COPE was used to assess coping methods. This study included 1134 respondents (age 21.76 ± 3.48 years; female 70.5%). Around 32% students reported having thoughts of death and/or self-harm in the past 2 weeks (several days 14.8%, over half the days 7.1%, and nearly every day 10.2%). Moreover, these thoughts were equally prevalent among the demographics. Suicidal ideation/self-harm was found to be increased by the severity of generalized anxiety and depression (p < 0.001). In conclusion, the rate of suicidal ideation/self-harm is alarmingly high in Pakistani university students during the COVID-19 pandemic. There is a dire need to initiate the psychological measures to prevent suicidal behaviors in Pakistani youth. Addressing mental health disparities and preparing support systems to mitigate mental health consequences as the pandemic evolves will continue to be needed urgently.