bluuebunny/crossref_metadata_2025 huggingface dataset:
PD09 A prospective study of outcomes of narrowband ultraviolet B for the treatment of paediatric atopic dermatitis, with additional breakdown by ethnicity/skin type
Authors: Sambi Pavan , Warburton Katharine , Montgomery Rachel , Majeethia Parisha , Thompson Mia , Clark Sheila
Published: June 2023

Narrowband UVB (NBUVB) phototherapy is regarded as a second-line treatment for atopic dermatitis (AD) when response to first-line treatment is ineffective. We undertook a prospective study evaluating response to NBUVB treatment in paediatric AD to assess changes to pretreatment Eczema Area and Severity Index (EASI) score immediately postphototherapy and 12 months later. We subanalysed response in different skin types. All patients had NBUVB treatment three times weekly up to a maximum of 40 exposures. Follow-up was every 3 months for 1 year postphototherapy. In total, 58 patients were recruited for NBUVB phototherapy treatment [37 (64%) men, 21 (36%) women, mean age 10.6 years (range 4.1–16.9 years)]. Skin types/ethnicity were as follows: White, n = 22 (38%); South Asian (Pakistani/Indian/Bangladeshi), n = 17 (29%); Black African/Caribbean, n = 9 (16%); other, n = 10 (17%). The immediate post-treatment mean EASI reductions vs. pretreatment baseline scores were 10.0 (entire cohort), 12.4 (White), 8.6 (South Asian), 2.5 (Black African/Caribbean) and 7.5 (other). A ≥ 75% increase in EASI (EASI 75) was achieved in the 49% of the entire cohort, in 48% of White people, in 50% of South Asians, in 44% of Black African/Caribbean people and in 56% of others. A ≥ 90% increase in EASI (EASI 90) was achieved in 15% of the whole group, 14% of White people, 13% of South Asians, 22% of Black African/Caribbean people and 11% of others. At 12 months post-treatment, mean EASI reduction vs. pretreatment baseline score was 7.6 in the whole cohort, 9.0 in White people, 8.6 in South Asians, −2.1 (i.e. worsening) in Black African/Caribbean people and 8.0 in others. At 12 months post-treatment, EASI 75 was achieved in 28% of the whole group, 33% of White people, 40% of South Asians, 14% of Black African/Caribbean people and 13% of others. For those who responded, there were a similar proportion of those achieving EASI 75 across the different skin types. However, there was more variation in the reduction in EASI score in those with skin colour. We acknowledge that existing scoring systems may lead to underscoring of the severity of erythema and therefore overall EASI score in darker skin types. Although the mean EASI reduction was highest in the group of White patients, there was a higher proportion of Black/Caribbean patients achieving EASI 90 at the end of the NBUVB treatment; however, the overall number of patients in this group was small. Our study showed that White and South Asian paediatric patients had a more sustained response to NBUVB phototherapy up to 1 year after stopping treatment. Black African/Caribbean patients had a greater risk of relapse.
BT20 Straight to biopsy vs. face-to-face consultation for skin lesions referred on a 2-week wait pathway: a review of outcomes
Authors: Brindley Luke , Hunjan Manrup , Walker Koharu , Higgins Kelly , Gazzani Paul
Published: June 2023

Teledermatology has become an essential tool in the triage and management of skin cancer referral pathways. The implementation of the process varies between dermatology departments. At a large multihospital trust, a retrospective service evaluation was conducted looking at the outcomes between two dermatology sites within the trust. Both use the same teledermatology platform to review all referrals made via a 2-week wait suspected cancer pathway for skin lesions. The main comparator was that one of the sites employs a straight to biopsy (STB) outcome as a potential pathway for referred lesions. The other site conducts face-to-face (F2F) review of suspicious lesions warranting biopsy first. Data were collected for all referrals made to both sites over a week in July 2021. A total of 506 lesions were referred across the two sites. Following teledermatology review at the site where STB was adopted, 32.2% (n = 96/298) of patients had a STB outcome and 33.9% (n = 101/298) had a F2F outcome. In comparison, 48.6% (n = 101/208) had a F2F outcome at the other site. Where STB was employed, biopsies were carried out for 13 intermediate lesions (actinic keratosis, superficial basal cell carcinoma, Bowen disease) vs. seven following F2F review at the other site. Rates of definitive surgery, for example wide local excision, were comparable between sites: 13.4% (STB) vs. 15.5%. Curettage and cautery was performed exclusively for lesions reviewed at the STB site, whereas at the other site, intermediate lesions were seen F2F and likely discharged following management with cryotherapy, topical treatments or conservative measures. The STB model can be appealing as it eliminates the need for a F2F review for lesions that require histological confirmation for diagnosis and management, saving valuable time and resources. However, the multiple stages involved in processing biopsies are costly and resource intensive when considering that many intermediate lesions can be treated from a clinical diagnosis alone. Biopsies are associated with increased morbidity and risk, unnecessary extra steps in patient care. With the Montgomery ruling, the process of consent must be robust and consider the individual values of each patient. Biopsies in more complex anatomical sites may pose additional difficulty when obtaining valid consent. The STB can have a role in the management of skin lesions and can streamline patient pathways. However, it does not replace good clinical acumen and, to remain cost-effective, needs to be employed in an appropriate manner.
BT23 Outcomes of skin lesion referrals assessed via teledermoscopy
Authors: Hamid Iman , Vandormael Isabelle , Mills Caroline , Atwan Ausama
Published: June 2023

Skin lesion referrals from primary care comprise a significant proportion of the dermatology workload. Urgent suspected cancer (USC) referrals are prioritized, which adds strain to outpatient capacity and impacts on waiting lists for less urgent and routine referrals. Our department provides a teledermoscopy diagnostic service to allow for timely diagnosis of skin lesions. This results in fast detection of USC and a reduction in unnecessary hospital visits for patients with benign lesions. The aim of this study was to review the outcomes of USC and routine referrals received from primary care and assessed via our teledermoscopy service. We randomly selected 381 skin lesion referrals triaged for teledermoscopy between January and March 2022. In total, 189 (49.6%) of these were referred as routine and 192 (50.4%) were urgent/USC. High-resolution clinical and dermoscopic photographs of all skin lesions were taken by qualified clinical photographers and stored in the patients’ electronic records. Two separate consultant dermatologists reviewed the images along with the information provided in the referrals for diagnosis. A total of 47 diagnoses were observed in both cohorts. Only 16% of patients referred as urgent/USC had suspected high-risk cancer, including squamous cell carcinoma (SCC; 8.8%), melanoma (5.7%) and lentigo maligna (1.5%). The remainder of urgent/USC referrals were identified as nonurgent or benign, with an overwhelmingly low risk of basal cell carcinoma (23.9%), seborrhoeic keratoses (20.8%) and benign naevi (9.3%). For routine referrals, 11 patients (5.8%) were suspected to have USC. Of these, five had histological confirmation of melanoma (n = 3), SCC (n = 1) and melanoma in situ (n = 1). Of all referrals, 44.6% were reassured and discharged; 20.8% required clinic review for a diagnostic biopsy or treatment; 20.7% were booked directly for minor surgery; 8.3% were referred to the community local enhanced services for the treatment of low-risk lesions on the torso and limbs; 1.3% were referred to other specialties; and 4.1% required digital monitoring by repeating photographs 3–6 months later. An ever-increasing prevalence of skin cancer, together with suboptimal dermatology training for primary care healthcare professionals, anxiety over misdiagnosing malignancy and pressure from anxious patients all contribute to the pressure on dermatology services. We have shown that a teledermoscopy service is a useful tool for triaging skin cancer referrals to maximize the utilization of outpatient capacity and ensure timely treatment for patients with USCs.
Who’s at the table: an exploration of community-based food security initiatives and structures in a north-central Canadian context
Authors: Healy Theresa , Callihoo Christine , Booth Annie L
Published: June 2023

This article examines food security initiatives and actors specific to a rural, remote and northern Canadian community, a context found throughout the world. Using a ‘snowball technique’ to identify experts and practitioners in local food security, we employed qualitative engagement methods to map initiatives, actors and gaps in regional food security. We identified concerns around the ability of the region to be food secure; we also found a lack of cross-sector communication and planning, challenges with a small group of committed actors facing isolation and burnout and a need to more broadly engage the community and political entities with limited awareness of rural and remote cultures and concerns. Facilitating better collaborations across multiple food security-related activities while honouring current and supporting current initiatives could enable those who know their communities, to address food insecurity collectively and collaboratively in a rural, remote and northern context.
Cardiorenal interactions in heart failure: insights from recent therapeutic advances
Authors: Damman Kevin , Testani Jeffrey
Published: June 2023

Heart failure is a syndrome that may develop when cardiovascular disease progresses or is insufficiently treated and associated with a poor quality of life, high mortality rates, and increased healthcare expenditures. Prevention and treatment of heart failure are therefore of utmost importance. New therapies in patients with cardiovascular disease have recently been shown to be effective in the prevention and sometimes treatment of heart failure, and additional research is underway. Specifically, in high-risk patients with either (a combination of) diabetes, chronic kidney disease, and/or heart failure, three specific drug classes [sodium–glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1-RAs), and non-steroidal mineralocorticoid receptor antagonists (MRAs)] have taken centre stage in therapeutic approach for these high cardiovascular risk patients. The commonality of these drugs is the finding that they improve cardiovascular and renal endpoints across the cardiorenal continuum and SGTL2i have already proved effective in all subtypes of heart failure, while we await data on non-steroidal MRA therapy in heart failure. The story may be different for GLP-1-RA in patients with established heart failure, but these drugs are effective in reducing cardiovascular events in patients with diabetes. Taken together, these new therapies advance the treatment and improve the associated outcomes of patients with cardiorenal disease and diabetes, with similar characteristics and effectiveness in different conditions.
Microbial roles in the terrestrial and aquatic nitrogen cycle—implications in climate change
Authors: Mattoo Rohini , B M Suman
Published: June 2023

Nitrogen, as an essential component for living organisms, is the primary limiting nutrient on Earth. The availability and effective utilization of nitrogenous compounds for metabolic and other essential biochemical reactions are dependent on the myriad and phylogenetically diverse microbial communities. The microorganisms harmoniously interact and participate in every reaction of the nitrogen cycle to continuously transform nitrogen into its various bio-available forms. Research on the nitrogen cycle continues to disclose that there are many reactions that remain unknown. In this review, we summarize the recent discoveries that have contributed to advancing our understanding of the microbial involvement in reactions of the nitrogen cycle in soil and aquatic systems that influence climate change. Additionally, the mini-review highlights, which anthropogenic activities cause disturbances in the nitrogen cycle and proposes how beneficial microbes may be harnessed to replenish nitrogen in agricultural ecosystems.
Species-specific protein–protein interactions govern the humanization of the 20S proteasome in yeast
Authors: Sultana Sarmin , Abdullah Mudabir , Li Jianhui , Hochstrasser Mark , Kachroo Aashiq H
Published: June 2023

Yeast and humans share thousands of genes despite a billion years of evolutionary divergence. While many human genes can functionally replace their yeast counterparts, nearly half of the tested shared genes cannot. For example, most yeast proteasome subunits are “humanizable,” except subunits comprising the β-ring core, including β2c (HsPSMB7, a constitutive proteasome subunit). We developed a high-throughput pipeline to humanize yeast proteasomes by generating a large library of Hsβ2c mutants and screening them for complementation of a yeast β2 (ScPup1) knockout. Variants capable of replacing ScPup1 included (1) those impacting local protein–protein interactions (PPIs), with most affecting interactions between the β2c C-terminal tail and the adjacent β3 subunit, and (2) those affecting β2c proteolytic activity. Exchanging the full-length tail of human β2c with that of ScPup1 enabled complementation. Moreover, wild-type human β2c could replace yeast β2 if human β3 was also provided. Unexpectedly, yeast proteasomes bearing a catalytically inactive HsPSMB7-T44A variant that blocked precursor autoprocessing were viable, suggesting an intact propeptide stabilizes late assembly intermediates. In contrast, similar modifications in human β2i (HsPSMB10), an immunoproteasome subunit and the co-ortholog of yeast β2, do not enable complementation in yeast, suggesting distinct interactions are involved in human immunoproteasome core assembly. Broadly, our data reveal roles for specific PPIs governing functional replaceability across vast evolutionary distances.
Olfactory Dysfunction and Depression Trajectories in Community-Dwelling Older Adults
Authors: Kamath Vidyulata , Jiang Kening , Manning Kevin J , Mackin R Scott , Walker Keenan A , Powell Danielle , Lin Frank R , Chen Honglei , Brenowitz Willa D , Yaffe Kristine , Simonsick Eleanor M , Deal Jennifer A
Published: June 2023

Background

We examined the relationship between baseline olfactory performance and incident significant depressive symptoms and longitudinal depression trajectories in well-functioning older adults. Inflammation and cognitive status were examined as potential mediators.

Methods

Older adults (n = 2 125, 71–82 years, 51% female, 37% Black) completed an odor identification task at Year 3 (our study baseline) of the Health, Aging, and Body Composition study. Cognitive assessments, depressive symptoms, and inflammatory markers were ascertained across multiple visits over 8 years. Discrete-time complementary log-log models, group-based trajectory models, and multivariable-adjusted multinomial logistic regression were employed to assess the relationship between baseline olfaction and incident depression and longitudinal depression trajectories. Mediation analysis assessed the influence of cognitive status on these relationships.

Results

Individuals with lower olfaction had an increased risk of developing significant depressive symptoms at follow-up (hazard ratio = 1.04, 95% confidence interval [CI]: 1.00, 1.08). Of the 3 patterns of longitudinal depression scores identified (stable low, stable moderate, and stable high), poorer olfaction was associated with a 6% higher risk of membership in the stable moderate (relative risk ratio [RRR] = 1.06, 95% CI: 1.02, 1.10)/stable high (RRR = 1.06, 95% CI: 1.00, 1.12) groups, compared to the stable low group. Poor cognitive status, but not inflammation, partially mediated the relationship between olfactory performance and incident depression symptom severity.

Conclusions

Suboptimal olfaction could serve as a prognostic indicator of vulnerability for the development of late-life depression. These findings underscore the need for a greater understanding of olfaction in late-life depression and the demographic, cognitive, and biological factors that influence these relationships over time.
A non-coding insertional mutation ofGrhl2causes gene over-expression and multiple structural anomalies including cleft palate, spina bifida and encephalocele
Authors: Crane-Smith Zoe , De Castro Sandra C P , Nikolopoulou Evanthia , Wolujewicz Paul , Smedley Damian , Lei Yunping , Mather Emma , Santos Chloe , Hopkinson Mark , Pitsillides Andrew A ,   Genomics England Research Consortium, Finnell Richard H , Ross M Elisabeth , Copp Andrew J , Greene Nicholas D E
Published: June 2023

Orofacial clefts, including cleft lip and palate (CL/P) and neural tube defects (NTDs) are among the most common congenital anomalies, but knowledge of the genetic basis of these conditions remains incomplete. The extent to which genetic risk factors are shared between CL/P, NTDs and related anomalies is also unclear. While identification of causative genes has largely focused on coding and loss of function mutations, it is hypothesized that regulatory mutations account for a portion of the unidentified heritability. We found that excess expression of Grainyhead-like 2 (Grhl2) causes not only spinal NTDs in Axial defects (Axd) mice but also multiple additional defects affecting the cranial region. These include orofacial clefts comprising midline cleft lip and palate and abnormalities of the craniofacial bones and frontal and/or basal encephalocele, in which brain tissue herniates through the cranium or into the nasal cavity. To investigate the causative mutation in the Grhl2Axd strain, whole genome sequencing identified an approximately 4 kb LTR retrotransposon insertion that disrupts the non-coding regulatory region, lying approximately 300 base pairs upstream of the 5’ UTR. This insertion also lies within a predicted long non-coding RNA, oriented on the reverse strand, which like Grhl2 is over-expressed in Axd (Grhl2Axd) homozygous mutant embryos. Initial analysis of the GRHL2 upstream region in individuals with NTDs or cleft palate revealed rare or novel variants in a small number of cases. We hypothesize that mutations affecting the regulation of GRHL2 may contribute to craniofacial anomalies and NTDs in humans.
Comprehensive analysis of autophagic functions of WIPI family proteins and their implications for the pathogenesis of β-propeller associated neurodegeneration
Authors: Shimizu Takahiro , Tamura Norito , Nishimura Taki , Saito Chieko , Yamamoto Hayashi , Mizushima Noboru
Published: June 2023

β-propellers that bind polyphosphoinositides (PROPPINs) are an autophagy-related protein family conserved throughout eukaryotes. The PROPPIN family includes Atg18, Atg21 and Hsv2 in yeast and WD-repeat protein interacting with phosphoinositides (WIPI)1–4 in mammals. Mutations in the WIPI genes are associated with human neuronal diseases, including β-propeller associated neurodegeneration (BPAN) caused by mutations in WDR45 (encoding WIPI4). In contrast to yeast PROPPINs, the functions of mammalian WIPI1–WIPI4 have not been systematically investigated. Although the involvement of WIPI2 in autophagy has been clearly shown, the functions of WIPI1, WIPI3 and WIPI4 in autophagy remain poorly understood. In this study, we comprehensively analyzed the roles of WIPI proteins by using WIPI-knockout (single, double and quadruple knockout) HEK293T cells and recently developed HaloTag-based reporters, which enable us to monitor autophagic flux sensitively and quantitatively. We found that WIPI2 was nearly essential for autophagy. Autophagic flux was unaffected or only slightly reduced by single deletion of WIPI3 (encoded by WDR45B) or WIPI4 but was profoundly reduced by double deletion of WIPI3 and WIPI4. Furthermore, we revealed variable effects of BPAN-related missense mutations on the autophagic activity of WIPI4. BPAN is characterized by neurodevelopmental and neurodegenerative abnormalities, and we found a possible association between the magnitude of the defect of the autophagic activity of WIPI4 mutants and the severity of neurodevelopmental symptoms. However, some of the BPAN-related missense mutations, which produce neurodegenerative signs, showed almost normal autophagic activity, suggesting that non-autophagic functions of WIPI4 may be related to neurodegeneration in BPAN.
Pre-entry knowledge base complexity and post-entry growth: evidence from Italian firms
Authors: Guerzoni Marco , Nuccio Massimiliano , Tamagni Federico
Published: June 2023

Knowledge is largely recognized as a key driver of survival and growth of new entrants. Previous literature on the role of pre-entry knowledge in post-entry performance has focused on entrepreneurial and managerial capabilities and education and on knowledge incorporated in material and immaterial resources. In this paper, taking to the firm level the intuition behind the notion of economic and technological complexity of countries, we hypothesize that post-entry performance of new firms may be explained by their knowledge base complexity, which captures the reinforcing mechanism between variety and creation of new valuable knowledge. We provide a measure of firm-level complexity derived from the analysis of textual content of patents and exploit it to examine the empirical relation between pre-entry complexity of knowledge and post-entry growth in a sample of Italian firms entering the market in 2009-2011. Baseline results show a significant and positive association between knowledge complexity and post-entry growth, even after controlling for firm characteristics and year, sector, and region fixed effects. Robustness analysis reveals that this positive effect is more significant over the medium run than in the initial years after entry, while relatively weaker for the so-called Innovative Small and Medium-Sized Enterprises.
A study on the perioperative effects of obesity on minimally invasive coronary artery bypass grafting and its surgical techniques
Authors: Liu Jia-Ji , Liang Lin , Kong Qing-Yu , Ma Xiao-Long , Chi Li-Qun , Lai Yong-Qiang
Published: June 2023

OBJECTIVES

The aim of this study was to discuss the perioperative effects of obesity on minimally invasive coronary artery bypass grafting (CABG) and its surgical techniques.

METHODS

A total of 582 patients with multivessel lesion who underwent off-pump CABG by our medical group of Beijing Anzhen Hospital between January 2017 and January 2021 were divided into the minimally invasive cardiac surgery (MICS) group and the conventional group (median sternotomy) according to the surgical method used. The body mass index of the patients was calculated, based on which both groups were divided into obese (≥28 kg/m2) and non-obese subgroups (<28 kg/m2). First, the perioperative data of the obese subgroups of both MICS and conventional groups were compared. Second, the obese and non-obese subgroups were compared in the MICS group.

RESULTS

Despite a higher proportion of diabetes in the MICS group, there was no significant difference in preoperative baseline nor in the incidence of major complications within 30 days after surgery between obese subgroups of the MICS and conventional groups. The MICS group had a significantly lower rate of poor wound healing, along with a higher predischarge Barthel Index. Also, the preoperative baseline between the obese and non-obese subgroups of the MICS group exhibited no statistical differences. The obese subgroup had longer postoperative ventilator assistance, while other intraoperative data and postoperative observation indexes exhibited no significant differences.

CONCLUSIONS

MICS CABG method is safe and feasible for obese patients with multivessel lesion. Minimally invasive surgery is beneficial to wound healing in obese patients. However, it requires a thorough preoperative evaluation and adequate surgical experience and skills.
Predicting the death of patients with anti-melanoma differentiation–associated protein-5-positive dermatomyositis-associated interstitial lung disease: A systematic review and meta-analysis
Authors: Yang Baolu , Liu Suying , Qian Zhenbei , Tong Zhaohui
Published: June 2023

Objectives

To investigate the risk factors for death in anti-melanoma differentiation–associated protein-5-positive dermatomyositis-associated interstitial lung disease (ILD).

Methods

Studies were identified by searching PubMed, Embase, Web of Science, and Cochrane Library. We calculated pooled risk ratios (RRs) or standardized mean differences (SMDs) and 95% confidence intervals (CIs) using random-effects models.

Results

Twenty studies were selected. Factors that may increase death risk included older age (SMD: 0.62, 95% CI: 0.42–0.81), elevated Krebs von den Lungen-6 (SMD: 0.66, 95% CI: 0.47–0.86), lactate dehydrogenase (SMD: 0.87, 95% CI: 0.72–1.02), C-reactive protein (SMD: 0.62, 95% CI: 0.44–0.80), ferritin (SMD: 0.93, 95% CI: 0.71–1.15), creatine kinase (SMD: 0.28, 95% CI: 0.13–0.44), neutrophil (SMD: 0.34, 95% CI: 0.04–0.64), neutrophil-to-lymphocyte ratio (SMD: 0.52, 95% CI: 0.24–0.79), aspartate aminotransferase (SMD: 0.70, 95% CI: 0.45–0.94), shorter disease duration (SMD: −0.44, 95% CI: −0.67 to −0.21), rapidly progressive ILD (RR: 4.08, 95% CI: 3.01–5.54), fever (RR: 1.98, 95% CI: 1.46–2.69), dyspnoea (RR: 1.63, 95% CI: 1.32–2.02), and anti-Ro52 antibody positive (RR: 1.28, 95% CI: 1.11–1.49). Female (RR: 0.86, 95% CI: 0.78–0.94), increased albumin (SMD: −1.20, 95% CI: −1.76 to −0.64), lymphocyte (SMD: −0.49, 95% CI: −0.67 to −0.30), and arthralgia (RR: 0.53, 95% CI: 0.37–0.78) were protective factors.

Conclusion

Older age, shorter disease duration, rapidly progressive ILD, fever, dyspnoea, anti-Ro52 antibody positive, and some inflammatory markers were risk factors for death in patients with anti-melanoma differentiation–associated protein-5-positive dermatomyositis-associated ILD.
Transitioning to Dolutegravir in a Programmatic Setting: Virological Outcomes and Associated Factors Among Treatment-Naive Patients With HIV-1 in the Kilombero and Ulanga Antiretroviral Cohort in Rural Tanzania
Authors: Ntamatungiro Alex J , Eichenberger Anna , Okuma James , Vanobberghen Fiona , Ndege Robert , Kimera Namvua , Francis Joel M , Kagura Juliana , Weisser Maja ,   for the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) Study Group
Published: June 2023

Background

Virological outcome data after programmatic transition from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based to dolutegravir (DTG)-based antiretroviral therapy (ART) regimens in sub-Saharan Africa (SSA) outside of clinical trials are scarce. We compared viral suppression and associated factors in treatment-naïve people living with HIV (PLHIV) starting DTG- based versus NNRTI-based ART.

Methods

We compared virological suppression at 12 months, after treatment initiation in the two cohorts of participants aged ≥15 years, initiating DTG- and NNRTI-based ART. Drug resistance was assessed among participants with viremia ≥50 copies/mL on DTG.

Results

Viral suppression was achieved for 165/195 (85%) and 154/211 (73%) participants in the DTG- and NNRTI- cohorts, respectively (P = 0.003). DTG-based ART was associated with >2 times the odds of viral suppression versus NNRTI-based ART (adjusted odds ratio, 2.10 [95% confidence interval {CI}, 1.12–3.94]; adjusted risk ratio, 1.11 [95% CI, 1.00–1.24]). HIV-1 genotypic resistance testing (GRT) before ART initiation was done in 14 of 30 viremic participants on DTG, among whom nucleoside reverse transcriptase inhibitor (NRTI), NNRTI, and protease inhibitors resistance was detected in 0 (0%), 2 (14%) and 1 (7%), respectively. No resistance was found in the 2 of 30 participants with available GRT at the time of viremia ≥50 copies/mL.

Conclusions

Virological suppression at 1 year was higher in participants initiating DTG- versus NNRTI-based ART. In those with viremia ≥50 copies/mL on DTG-based ART, there was no pretreatment or acquired resistance to the DTG co-administered NRTIs, although the number of samples tested was small.
Strawson’s Account of Morality and its Implications for Central Themes in ‘Freedom and Resentment’
Authors: De Mesel Benjamin , Cuypers Stefaan E
Published: June 2023

We argue that P. F. Strawson's hugely influential account of moral responsibility in ‘Freedom and Resentment’ (FR) is inextricably bound up with his barely known account of morality in ‘Social Morality and Individual Ideal’ (SMII). Reading FR through the lens of SMII has at least three far-reaching implications. First, the ethics–morality distinction in SMII gives content to Strawson's famous distinction between personal and moral reactive attitudes, which has often been thought to be a merely formal distinction. Second, the ethics–morality distinction sheds light on the scope of moral responsibility in FR, which is narrower than commentators think. Third, Strawson's discussion of morality shows that he was not insensitive to issues of power, as several critics have claimed. The link between morality and power helps to make clear that Strawson allows for criticism of our moral responsibility practices.
Associations Between Childhood Area-Level Social Fragmentation, Maladaptation to School, and Social Functioning Among Healthy Youth and Those at Clinical High Risk for Psychosis
Authors: Ku Benson S , Addington Jean , Bearden Carrie E , Cadenhead Kristin S , Cannon Tyrone D , Compton Michael T , Cornblatt Barbara A , Druss Benjamin G , Gülöksüz Sinan , Mathalon Daniel H , Perkins Diana O , Tsuang Ming T , Walker Elaine F , Woods Scott W , Carrión Ricardo E
Published: June 2023

Background and Hypothesis

Although studies have identified social fragmentation as an important risk factor for schizophrenia and other psychotic disorders, it is unknown whether it may impact social functioning. This study investigates whether social fragmentation during childhood predicts maladaptation to school as well as social functioning during childhood and adulthood.

Study Design

Data were collected from the North American Prodrome Longitudinal Study. Participants included adults at clinical high risk for psychosis (CHR-P) and healthy comparisons (HC). Maladaptation to school and social functioning during childhood were assessed retrospectively and social functioning in adulthood was assessed at baseline.

Study Results

Greater social fragmentation during childhood was associated with greater maladaptation to school (adjusted β = 0.21; 95% CI: 0.02 to 0.40). Social fragmentation was not associated with social functioning during childhood (unadjusted β = −0.08; 95% CI: −0.31 to 0.15). However, greater social fragmentation during childhood predicted poorer social functioning in adulthood (adjusted β = −0.43; 95% CI: −0.79 to −0.07). Maladaptation to school mediated 15.7% of the association between social fragmentation and social functioning. The association between social fragmentation and social functioning was stronger among adults at CHR-P compared to HC (adjusted β = −0.42; 95% CI: −0.82 to −0.02).

Conclusions

This study finds that social fragmentation during childhood is associated with greater maladaptation to school during childhood, which in turn predicts poorer social functioning in adulthood. Further research is needed to disentangle aspects of social fragmentation that may contribute to social deficits, which would have implications for the development of effective interventions at the individual and community levels.
Perioperative anaphylaxis: when the allergological work-up goes negative
Authors: Mertes Paul-Michel , Tacquard Charles
Published: June 2023

Purpose of review

Perioperative anaphylaxis (POA) is rare but is associated with significant morbidity and mortality. Patients are referred to the allergist to identify the mechanism of the reaction, the causative agent and make recommendations regarding subsequent anaesthesia. Despite a well conducted allergological evaluation, the causative agent is not found in 30–60% of these reactions, leaving patients without a well established diagnosis.

Recent findings

Several mechanisms can induce POA. In addition to the well known IgE-mediated reactions, IgG-mediated reaction, MRGPR-X2-related reaction or nonspecific histamine release may be involved. These situations are not easily assessed by the allergological workup.

When the allergological workup is negative, the situation should be reassessed with the team present at the time of the reaction to confirm the reality of the hypersensitivity reaction and to search for a possible differential diagnosis. If POA is confirmed, the allergological evaluation should be repeated, ensuring proper execution according to current guidelines and including the search for hidden allergens. Specific IgE assays or basophil activation tests may be of interest. In case of negative results, a closely monitored drug challenge test, in coordination with the anaesthesia teams, may be useful to avoid the exclusion of any drug injected during the reaction.
Drug allergy in primary care: systematic review to support quality improvement initiative of management and optimization of healthcare pathways
Authors: Gaudin Clara , Ryan Dermot , Demoly Pascal , Tanno Luciana Kase
Published: June 2023

Purpose of review

The aim of this study was to review the practice of general practitioners (GPs) in regard to the diagnosis and management of drug hypersensitivity reactions (DHRs) to identify major challenges and to facilitate the development of decision support tools to GPs confronted with DHRs patients.

Recent findings

DHRs are still a challenge in the GPs clinical practice, which implies difficulties in clinical decisions and referral to allergy specialists.

DHRs can range from mild to severe and even life-threatening. Drugs are the main cause of anaphylaxis deaths in most countries. Most DHRs are firstly seen by GPs, paediatricians or emergency doctors. However, our systematic review demonstrated difficulties in differentiating DHRs from other drug side effects. Most DHRs epidemiological data are from hospital and emergency departments, which may not reflect the real-life experience in primary care. GPs should be aware of the alert signs of DHRs: the involvement of other systems beyond the skin and/or atypical skin/ mucosal involvement, which mandated immediate referral to an emergency department. Data still stress difficulties in the recognition of DHRs clinical manifestations and highlight the need for decision aids to support their management by GPs. Structured clinical history and clinical examination are key diagnostic tools. Reasons for referring to allergy specialists based on the literature are to investigate cause, to undergo specific procedure, such as desensitization and to identify well tolerated, alternative drugs.
Association of ambient air pollution and cardiovascular symptoms: a systematic review and meta-analysis
Authors: Zhou Shiyu , Liu Fangchao , Liu Hanrui , Huang Sihan , Lu Xiangfeng , Huang Jianfeng
Published: June 2023

Background and purpose:

Cardiovascular disease is the leading cause of disease burden globally. Previous studies have suggested that air pollution is a risk factor for cardiovascular symptoms, however, the results are controversial. Thus, we conducted this study to systematically review available evidence quantifying the relationship between exposure to ambient gaseous and particulate air pollutants and cardiovascular symptoms.

Methods:

Three databases were searched up to September 10, 2022, for articles investigating the association of air pollutants including sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide, and particulate matter with aerodynamic diameters of ≤10 μm and ≤2.5 μm (PM10 and PM2.5) with cardiovascular symptoms of chest pain, shortness of breath, respiratory distress, and palpitation. Random-effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (95% CI) for chest pain in association with PM2.5. Egger test was used to assess publication bias in the included studies.

Results:

Of the 16 studies that were included in the systematic review, 10 were used to calculate the pooled OR for chest pain. Most of them were from developed countries, where air pollution levels were relatively low. Short-term exposure to air pollutants may increase the risk of chest pain, with the pooled OR 1.016 (95% CI 1.003–1.030) per 10 μg/m³ increment of PM2.5.

Conclusions:

Air pollution is a potential risk factor for cardiovascular symptoms, especially chest pain. However, most current studies are conducted in low-pollution regions. More studies from high-pollution regions are needed to confirm the role of ambient air pollution in cardiovascular symptoms and reveal the underlying health effects.
Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma
Authors: Lejeune Margaux , Köse Murat Cem , Jassin Mégane , Gou Marie-Jia , Herbet Amaury , Duray Elodie , Cobraiville Gaël , Foguenne Jacques , Boquet Didier , Gothot André , Beguin Yves , Fillet Marianne , Caers Jo
Published: June 2023

Despite the recent introduction of next-generation immunotherapeutic agents, multiple myeloma (MM) remains incurable. New strategies targeting MM-specific antigens may result in a more effective therapy by preventing antigen escape, clonal evolution, and tumor resistance. In this work, we adapted an algorithm that integrates proteomic and transcriptomic results of myeloma cells to identify new antigens and possible antigen combinations. We performed cell surface proteomics on 6 myeloma cell lines based and combined these results with gene expression studies. Our algorithm identified 209 overexpressed surface proteins from which 23 proteins could be selected for combinatorial pairing. Flow cytometry analysis of 20 primary samples confirmed the expression of FCRL5, BCMA, and ICAM2 in all samples and IL6R, endothelin receptor B (ETB), and SLCO5A1 in >60% of myeloma cases. Analyzing possible combinations, we found 6 combinatorial pairs that can target myeloma cells and avoid toxicity on other organs. In addition, our studies identified ETB as a tumor-associated antigen that is overexpressed on myeloma cells. This antigen can be targeted with a new monoclonal antibody RB49 that recognizes an epitope located in a region that becomes highly accessible after activation of ETB by its ligand. In conclusion, our algorithm identified several candidate antigens that can be used for either single-antigen targeting approaches or for combinatorial targeting in new immunotherapeutic approaches in MM.
Conjunctival Microbiota and Blepharitis Symptom Scores in Patients With Ocular Rosacea
Authors: Mergen Burak , Onal Irem , Gulmez Abdurrahman , Caytemel Ceyda , Yildirim Yusuf
Published: June 2023

Purpose:

Investigation of the relationship between blepharitis-related symptom scores, tear film functions, and conjunctival microbiota in patients with ocular rosacea (OR) compared with healthy controls was aimed.

Methods:

Consecutive 33 eyes of 33 patients with OR who were admitted from the dermatology clinic and age-matched and gender-matched 30 healthy controls were included in the study. Tear breakup time (TBUT), Schirmer score, and blepharitis symptom score (BLISS) were recorded for each patient. For the bacteriological examination, bacterial culture was obtained by inoculating the samples on chocolate agar, blood agar, and fluid thioglycollate medium. The growth of different colonies of bacteria was identified using matrix-assisted laser desorption or ionization time-of-flight mass spectrometry.

Results:

Bacterial culture positivity was observed in 13 eyes (39.4%) in the patients with OR and 10 eyes (33.3%) in the controls (P=0.618). Patients with OR showed worse TBUT and Schirmer scores, and higher BLISSs (P=0.005, P=0.007, and P=0.001, respectively). Patients with OR with conjunctival culture-positive results showed higher BLISSs (8.0±4.7) compared with those with negative results (4.7±2.3; P<0.001). The most frequent bacteria was Micrococcus luteus (18.2%) in patients with OR and Staphylococcus epidermidis (20.0%) in the controls.

Conclusion:

This pilot study showed that patients with OR had similar conjunctival culture positivity compared with healthy controls. However, the observation of different dominant bacterial species in conjunctival microbiota and the observation of worse BLISSs in patients with OR with positive culture might suggest a potential role of conjunctival microbiota in the pathogenesis of OR.
Occult Cytomegalovirus Cholangitis and Pancreatic Adenocarcinoma
Authors: Mastroianni Antonio , Greco Sonia , Vangeli Valeria , Mauro Maria Vittoria , Greco Francesca , Manfredi Roberto
Published: June 2023

A rare case of occult cytomegalovirus (CMV) cholangitis along with an updated literature review is presented. The patient had not undergone solid organ–bone marrow transplantation and had no chronic autoimmune biliary tract disorder or obvious immunodeficiency. The patient had underwent a pyloric-sparing duodenocephalopancreasectomy, and the postoperative histopathologic examination revealed multiple ulcerative lesions and an occult CMV infection. The copy number of CMV DNA was high (38,000 copies/μg DNA) in common bile duct surgical specimens measured by real-time quantitative polymerase chain reaction. CMV was not detected in blood and urine samples from the patient after full doses of intravenous ganciclovir and full doses of oral valganciclovir antiviral therapy. This report recapitulates the role of CMV in causing severe cholangiopathy in the absence of obvious immunosuppression or autoimmune disorder of the biliary tract.
Safety and Efficacy of SARS-CoV-2 Vaccination in Patients With Chronic Liver Disease
Authors: Mao Yu-Feng , Gao Lin , Li Yuan-Yuan , Wang Fu-Sheng
Published: June 2023

Patients with chronic liver diseases (CLDs) have high hospitalization and mortality rates when combined with severe coronavirus disease 2019 (COVID-19) because of defects in humoral and cellular immunity, known as immune dysfunction. COVID-19 vaccines effectively reduce the risk of severe illness and mortality caused by the virus. Several studies have confirmed the safety and efficacy of the COVID-19 vaccine in patients with CLD, and the existing expert consensus recommends that patients with stable CLD be prioritized for the COVID-19 vaccine. In addition, clinical trials are ongoing to determine the optimal strategy for patients with CLD to receive the COVID-19 vaccine. In this study, we review the progress of research on the safety and efficacy of COVID-19 vaccination in patients with CLD, aiming to provide better recommendations for the vaccination in this population.
Fatal Thyroid Storm in the Setting of Untreated Graves Disease and Use of the Synthetic Cannabinoid MDMB-4en-PINACA
Authors: Ricciardo Sean , Hastings Stephen
Published: June 2023

Thyroid storm, or thyrotoxic crisis, is a rare but well-described and potentially lethal exacerbation of thyrotoxicosis, characterized by multisystem effects due to failure of the hypothalamic-pituitary-thyroid axis. Thyroid storm is seen most frequently in the setting of inadequately treated Graves disease; however, it may also be triggered or exacerbated by infection, trauma, childbirth, radioiodine treatment, and pharmacologic agents. While there are rare reports of cases in which illicit drug use may have triggered or exacerbated thyroid storm, none specifically involving synthetic cannabinoids have been previously described. We present the case of a 25-year-old man who presented with thyroid storm in the setting of poorly controlled Graves disease and synthetic cannabinoid use.
Gastric Glandular Siderosis but not Lamina Propria Siderosis is Associated With High Serum Ferritin Levels
Authors: Sarwate Mrinal , Khaitan Neha , Alpert Lindsay , Tavberidze Nika , Zhang Wei , Panarelli Nicole , Hu Shaomin
Published: June 2023

Three histologic patterns of gastric siderosis (GS) are described: pattern A (predominantly in lamina propria stromal cells—gastric lamina propria siderosis [GLPS]), pattern B (mostly extracellular crystalline iron) and pattern C (predominantly in glandular epithelium—gastric glandular siderosis [GGS]). This study aimed to analyze the association of GGS with clinicopathologic features using 3 cohorts. Cohort #1 consisted of 76 gastric siderosis cases. Upon classifying the cases into 3 groups by percentage of glandular involvement (negative, 1% to 5%, ≥5% GGS), the degree of GGS was positively associated with serum ferritin levels (P=0.002), transferrin saturation (P=0.003), and history of blood transfusion (P=0.009). After excluding cases with coarse extracellular crystalline iron, cohort #1 was reclassified into 3 groups by degree of GLPS (no, rare [discernible at ×20 or ×40], overt [readily visible at low power]). The degree of GLPS was positively correlated with oral iron pill use (P=0.01), but not serum ferritin levels or transferrin saturation. Cohort #2 contained 31 gastric samples from patients with hereditary hemochromatosis, most received phlebotomy treatment. GGS was identified in 2 (6.4%) patients; both had high ferritin levels. Cohort #3 included 38 gastric samples from patients with cirrhosis. Three (8%) cases showed GGS; serum ferritin level was available for 1 case and was elevated. These results indicate that GGS is associated with systemic iron overload, while GLPS is correlated with oral iron pill use. The identification of GGS, especially when it’s ≥5%, should trigger further workup for potential systemic iron overload and underlying etiologies.
Hepatic Angiosarcomas With Sinusoidal Growth Patterns
Authors: Soon Gwyneth S.T. , Chen Zongming Eric , Wu Tsung-Teh , Torbenson Michael S. , Yasir Saba
Published: June 2023

Hepatic angiosarcomas are aggressive malignant tumors of the liver with variable morphology. One of the rare morphologies is that of the sinusoidal growth pattern, which is challenging to diagnose because of its subtle imaging and morphologic findings. This retrospective study characterizes the clinical, histologic, and immunohistochemical features of sinusoidal hepatic angiosarcomas. Thirteen cases were included in the study, comprising 12 (92.3%) needle core biopsies and 1 wedge biopsy; one of the needle biopsies also had a subsequent resection specimen available for review. Multiple biopsies were needed to make the diagnosis in 4 cases. At least moderate sinusoidal dilatation was seen in 53.8% of cases. Increased cellularity within the sinusoids was seen at both low-power and high-power magnification (69.2% and 84.6%, respectively). Cytologic atypia ranged from mild to marked. Multinucleated tumor cells were present in most cases (10/13 cases) but were often sparse. Mitotic activity was identified in 5/13 cases. ERG immunostains were more reliable than CD31 and CD34 in identifying the tumor cells. Ki-67 proliferative index ranged from 5% to 30%. p53 immunostains were available in 9 cases and c-MYC in 7 cases; they were positive in 62.5% and 33.3% of cases, respectively and had a mutually exclusive staining pattern. In summary, this rare pattern of hepatic angiosarcoma is challenging to diagnose but has distinctive morphologic findings that can be supplemented with immunostains to establish the diagnosis.