bluuebunny/crossref_metadata_2025 huggingface dataset:
The search finds an end: the morphologically chimeric hysterocinetids belong to the subclass Hymenostomatia (Ciliophora: Oligohymenophorea)
Authors: Obert Tomáš , Zhang Tengyue , Vďačný Peter
Published: June 2023

The digestive tract of oligochaetes harbours a diverse ciliate community embracing plagiotomids, nyctotherids, astomes, and hysterocinetids. Although several hundred intestinal ciliate species are known, only two hysterocinetids have been reported from the intestine of Holarctic lumbricid earthworms hitherto. The present study is focused on the taxonomy, morphology, and molecular phylogeny of two lumbricid-dwelling taxa, the insufficiently known Protoptychostomum simplex and Hysterocineta bellerophon sp. nov., detected in Central Europe. Diagnoses of the genera Protoptychostomum and Hysterocineta were improved taking into account also features of the oral ciliature for the first time. In the past, the proper classification of hysterocinetids in the class Oligohymenophorea was hampered by the dramatic remodelling of the anterior body end into a thigmotactic sucker, as well as by the helicalization and transfer of the oral apparatus to the posterior body pole. The present phylogenetic analyses of nuclear and mitochondrial genes robustly reject the classification of hysterocinetids in subclass Scuticociliatia or as a distinct subclass, Hysterocinetia. However, hysterocinetids were consistently and robustly nested deep in subclass Hymenostomatia in a sister-position to the free-living Tetrahymena paravorax. The hymenostome affinity of hysterocinetids is also corroborated by the parakinetal stomatogenesis and the stichodyad paroral membrane accompanied by three regularly organized membranelles.
The Self-Stigma of Hearing Loss in Adults and Older Adults: A Systematic Review
Authors: da Silva Jamile Cabral , de Araujo Cristiano Miranda , Lüders Debora , Santos Rosane Sampaio , Moreira de Lacerda Adriana Bender , José Maria Renata , Guarinello Ana Cristina
Published: June 2023

Objectives:

Previous studies have demonstrated that individuals with hearing loss can internalize social stigmas, resulting in several self-perceived negative connotations, such as incompetence, cognitive impairment, and social disability. This systematic review aimed to investigate the impact of the social stigma associated with hearing loss on the self-stigma experienced by adults and older adults.

Design:

Combinations of words and appropriate truncations were selected and adjusted specifically for each electronic database. The Population, Exposure, Comparator, Outcomes, and Study Characteristics strategy was used to delimit the scope of the review, bearing in mind the importance of a well-formulated research question.

Results:

A total of 953 articles were retrieved from the final search of each database. Thirty-four studies were selected for full-text reading. Thirteen were excluded, and 21 studies were ultimately included in this review. The results of this review were divided into three themes: (1) impact of social stigmas on self-stigma, (2) effect of emotions on self-stigma, and (3) other factors that impact self-stigma. The themes were related to the relationship between the individual and social perceptions reported by the participants with respect to their hearing experiences.

Conclusions:

Our results suggest that the impact of social stigma associated with hearing loss on the self-stigma of adults and older adults is strongly associated with the effects of aging and hearing loss, which may lead to withdrawal, social segregation, and negative self-perception.
Anterior Cervical Discectomy and Fusions Supplemented With Cellular or Noncellular Allografts Have Similar Radiographic Fusion and Clinical Outcomes
Authors: Zakko Philip , Blankenship Andrew , Jawad Ali , Kasir Rafid , Lee Maximillian , Park Daniel
Published: June 2023

Study Design:

A retrospective, single-center study.

Objective:

The aim of this study was to assess radiographic fusion after anterior cervical discectomy and fusion (ACDF) supplemented with either demineralized bone matrix or ViviGen in a polyetheretherketone biomechanical interbody cage.

Summary of Background Data:

Cellular and noncellular allografts are utilized as adjuncts in attempts to improve fusion after ACDF. The purpose of this study was to assess radiographic fusion and clinical outcomes after ACDF supplemented with cellular or noncellular allografts.

Materials and Methods:

A single surgeon’s clinical practice database was interrogated for consecutive patients who underwent a primary ACDF using cellular or noncellular allograft from 2017 to 2019. These subjects were matched by age, sex, body mass index, smoking status, and levels operated. Patient demographic and preoperative and postoperative patient-reported outcome measures (PROMs) including Visual Analog Scale Pain, Neck Disability Index, EuroQol-5 Dimension (EQ-5D), Patient-Reported Outcomes Measurement Information System (PROMIS), and Eating Assessment Tool 10 were collected preoperatively and at 3, 6, and 12 months postoperatively. Radiographic evidence of fusion was determined by <2 mm motion between spinous processes on flexion and extension radiographs and assessing bony bridging at 3, 6, and 12 months postoperatively.

Results:

There were 68 total patients, with 34 patients in each group, and 69 and 67 operative levels in the cellular and noncellular allograft groups, respectively. There was no difference in age, sex, body mass index, or smoking status between groups (P>0.05). There was no difference in number of 1-level, 2-level, 3-level, or 4-level ACDFs between cellular and noncellular groups (P>0.05). At 3, 6, and 12 months postoperatively, there was no difference in the percent of operated levels with <2 mm motion between spinous processes, complete bony bridging, or both <2 mm motion and complete bony bridging in the cellular and noncellular groups (P>0.05). There was no difference in the number of patients fused at all operated levels at 3, 6, or 12 months postoperatively (P>0.05). No patient required revision ACDF for symptomatic pseudarthrosis. There was no significant difference in PROMs between the cellular and noncellular groups at 12 months postoperatively except for improved EQ-5D and PROMIS-physical in the cellular compared with noncellular group (P=0.03).

Conclusions:

Similar radiographic fusion rates were achieved with cellular and noncellular allografts at all operated levels with similar PROMs in the cellular and noncellular groups at 3, 6, and 12 months postoperatively. Thus, ACDFs supplemented with cellular allograft demonstrate adequate radiographic fusion rates when compared with noncellular allografts with similar patient outcomes.

Level of Evidence:

Level III.
Role of Nuclear Receptor Subfamily 1 Group D Member 1 in the Proliferation, Migration of Vascular Smooth Muscle Cell, and Vascular Intimal Hyperplasia
Authors: Wang Mingliang , Qiu Chenming , Pan Quanrong , Yang Yongjian , Yang Dachun , Sun Xiongshan
Published: June 2023

Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) cause neointimal hyperplasia after percutaneous vascular interventions. Nuclear receptor subfamily 1 group D member 1 (NR1D1), a crucial member of circadian clock, is involved in the regulation of atherosclerosis and cellular proliferation. However, whether NR1D1 affects vascular neointimal hyperplasia remains unclear. In this study, we found that activating NR1D1 reduced injury-induced vascular neointimal hyperplasia. Overexpression of NR1D1 reduced the number of Ki-67-positive VSMCs and migrated VSMCs after platelet-derived growth factor (PDGF)-BB treatment. Mechanistically, NR1D1 suppressed the phosphorylation of AKT and 2 main effectors of the mammalian target of rapamycin complex 1 (mTORC1), S6, and 4EBP1 in PDGF-BB-challenged VSMCs. Re-activation of mTORC1 by Tuberous sclerosis 1 siRNA (siTsc1) and re-activation of AKT by SC-79 abolished NR1D1-mediated inhibitory effects on proliferation and migration of VSMCs. Moreover, decreased mTORC1 activity induced by NR1D1 was also reversed by SC-79. Simultaneously, Tsc1 knockdown abolished the vascular protective effects of NR1D1 in vivo. In conclusion, NR1D1 reduces vascular neointimal hyperplasia by suppressing proliferation and migration of VSMCs in an AKT/mTORC1-dependent manner.
Clear Cell Hidroacanthoma Simplex: A Case Report
Authors: Shao Ya-Kun , Chang Jian-Min
Published: June 2023

Introduction:

Hidroacanthoma simplex (HAS) is a benign eccrine adnexal neoplasm without characteristic clinical manifestations. Histopathologically, basaloid and poroid cell nests with ductal structure constitute the gold standard for diagnose.

We herein report a extremely rare subtype of HAS with clear cell infiltration under hematoxylin-eosin staining.

Case presentation:

A 70-year-old woman gradually developed an asymptomatic proliferative lesion for 4 years. The tumor was surgically removed without recurrence. Histopathologic results showed intraepidermal poroid cell nests with lumina-like structures. While, cells in the center of the tumor showed obvious abnormal transparency of the cytoplasm, forming clear cells. PAS glycogen staining showed diffusely positive.

Discussion:

Hidroacanthoma simplex is an intraepidermal epithelioma, forming by acanthotic epidermis and cystic or ductal structure. Theoretically, HAS tumor cells lack of the ability to secrete cellular glycogen and lipid, and thus cannot further form clear cells. Thus, the initiating factor of its generation and its meaning of existence need to be further discussed. Besides, diseases requiring identification are also listed in detail.

Conclusion:

Clear cell hidroacanthoma simplex is a rare pathological subtype of HAS. Raising awareness of its various differential diagnoses, minimizing the possibility of misdiagnosis become important for dermatologists.
Quality and Safety Practices Among Academic Obstetrics and Gynecology Departments
Authors: Christopher Diane , Leininger William M. , Beaty Laurel , Nunziato Jaclyn D. , Kremer Mallory E. , Diaz Quinones Juan J. , Rutz Sara , Griffin Todd R. , Klatt Timothy E.
Published: June 2023

The objective was to quantify resources devoted to quality and patient safety initiatives, to document the development and use of key performance indicator reports regarding patient outcomes and patient feedback, and to assess the culture of safety within academic obstetrics and gynecology departments. Chairs of academic obstetrics and gynecology departments were asked to complete a quality and safety assessment survey. Surveys were distributed to 138 departments, yielding 52 completed responses (37.7%). Five percent of departments reported including a patient representative on a quality committee. Most committee leaders (60.5%) and members (67.4%) received no compensation. Formal training was required in 28.8% of responding departments. Most departments monitored key performance metrics for inpatient outcomes (95.9%). Leaders scored their departments’ culture of safety highly. Most departments provided no protected time to faculty devoted to quality efforts, generation of key performance indicators for inpatient activities was prevalent and integrating patient and community input remain unrealized opportunities.
Cost-utility analysis of diagnostic methods for arterial hypertension in primary care for Brazil: ABPM vs. OBPM vs. HBPM
Authors: Garcia Rosana Lima , Silva Marcus Tolentino , Amaral Amaury Zatorre , Silva Giovanio Vieira
Published: June 2023

Introduction

Arterial hypertension (AH) is diagnosed using three methods: office blood pressure measurement (OBPM), home blood pressure monitoring (HBPM), and ambulatory blood pressure monitoring (ABPM). No economic studies have evaluated the impact of incorporating these strategies for AH diagnosis into the Brazilian public health system.

Methods

A Markov model was created to evaluate the costs associated with AH diagnosis using the ABPM, HBPM, and OBPM. Patients were entered into the model with SBP ≥ 130 mmHg or DBP ≥ 85 mmHg obtained using OBPM. The model was based on cost, quality adjusted life-years (QALYs), and incremental costs per QALY. In the economic analysis, the costs were calculated from the perspective of the payer of the Brazilian public health system.

Results

In the cost-utility analysis of the three methods, ABPM was the most cost-effective strategy compared to HBPM and OBPM in all groups over 35 years of age. Compared with OBPM, ABPM was a cost-effective strategy, as it presented higher costs in all scenarios, but with better QALYs. Compared to HBPM, ABPM was the dominant strategy for all age groups, presenting lower costs and higher QALYs. When comparing HBPM with OBPM, the results were similar to those described for ABPM (i.e. it was a cost-effective strategy).

Conclusion

With a willingness-to-pay threshold of R$35 000 per QALY gained, both ABPM and HBPM are cost-effective methods compared with OBPM in all scenarios. In Brazilian healthcare facilities that currently diagnose AH using OBPM, both ABPM and HBPM may be more cost-effective choices.
Medication safety in chronic kidney disease
Authors: Singh Sonal
Published: June 2023

Purpose of review

Several drugs cause nephrotoxicity and accelerate progression of chronic kidney disease (CKD). The objective of this review is to summarize recent evidence on drugs that either increase the risk of nephrotoxicity, progression of CKD or drug induced harm in patients with CKD.

Recent findings

Bisphosphonates and hypnotics increase the progression of CKD, whereas denosumab does not accelerate progression of CKD. Tenofovir disoproxil fumarate (TDF) increases the risk of renal tubular toxicity and adverse effects on bone, but Tenofovir alafenamide (TAF) and Tenofovir amibufenamide (TMF) have favorable safety profile on the kidneys and bones. Although no dosage adjustment is needed for Oral Nirmatrelvir/Ritonavir in patients with mild renal impairment and coronavirus disease 2019, the dosage is reduced to twice daily in those with moderate renal impairment. It is not recommended in patients with severe renal impairment. The prescribing information does not recommend use of remdesevir below glomerular filtration rate (eGFR) < 30 ml/min but recent studies suggest that remdesevir may be safe and effective in patients with varying levels of CKD severity. Molnupiravir does not require dose adjustment in patients with CKD.

Several medications increase the risk of development of acute kidney injury or progression of CKD. Close attention is needed to select the appropriate dose or safer alternatives to reduce the risk of drug-induced harm in patients with CKD.
Sex differences in renal electrolyte transport
Authors: McDonough Alicia A. , Layton Anita T.
Published: June 2023

Purpose of review

Women experience unique life events, for example, pregnancy and lactation, that challenge renal regulation of electrolyte homeostasis. Recent analyses of nephron organization in female vs. male rodent kidneys, revealed distinct sexual dimorphisms in electrolyte transporter expression, abundance, and activity. This review aims to provide an overview of electrolyte transporters’ organization and operation in female compared with the commonly studied male kidney, and the (patho)physiologic consequences of the differences.

Recent findings

When electrolyte transporters are assessed in kidney protein homogenates from both sexes, relative transporter abundance ratios in females/males are less than one along proximal tubule and greater than one post macula densa, which is indicative of a ‘downstream shift’ in fractional reabsorption of electrolytes in females. This arrangement improves the excretion of a sodium load, challenges potassium homeostasis, and is consistent with the lower blood pressure and greater pressure natriuresis observed in premenopausal women.

We summarize recently reported new knowledge about sex differences in renal transporters: abundance and expression along nephron, implications for regulation by Na+, K+ and angiotensin II, and mathematical models of female nephron function.
Technology Innovation and Disruption in Plastic Surgery: Intelligence Quotient, Emotional Quotient, and Technology Quotient
Authors: Jeffers Lynn L. C. , Sacks Justin M. , Kinney Brian M.
Published: June 2023

This article is an introduction to the new PRS Tech Disruptor Series, the culmination of work originating from the Technology Innovation and Disruption Presidential Task Force. Our technology quotient is important to our success as individuals and as a specialty society. The goal of this new series is to address the broader concepts in technology as they relate to plastic surgery and thus enhance the technology quotient of readers and, in turn, of the specialty and specialty society. Critical topics related to technology, their current and future impact on plastic surgery, and the opportunities and barriers in research, education, and advocacy will be addressed. The intent is for readers to engage in dialogue and think outside the box about the current and future impact of technology.
Advances in Open Reduction and Internal Fixation of Multiple Mandibular Fractures with Condylar Involvement
Authors: Bottini Gian Battista , Gaggl Alexander , Brandtner Christian
Published: June 2023

Multiple mandibular fractures with condylar involvement are challenging to treat. This article presents a series of steps to simplify the treatment and improve the outcomes in open reduction and internal fixation of multiple mandibular fractures with condylar involvement. Four new elements are identified: three-dimensional printing, model surgery, Kirschner wires to manipulate the segments in condylar fractures, and a top-to-bottom sequence. This algorithm has contributed to streamlining the procedure and improving the outcomes of these challenging fractures. For the same operator, reduction and osteosynthesis require approximately 40 minutes less than before the adoption of the new protocol. The authors have not encountered suboptimal reductions or situations where the screws were too long, necessitating exchange for shorter ones in revision surgery.
Utilizing Virtual Surgical Planning and Patient-Specific Cutting Guides in Microtia Repair with Autologous Costal Cartilage Graft
Authors: Pool Christopher , Moroco Annie , Lighthall Jessyka G.
Published: June 2023

Virtual surgical planning (VSP) has been applied to many aspects of head and neck reconstruction. The authors describe the use of VSP to create auricular templates in addition to cartilage cutting and suturing guides for microtia repair in 2 patients with unilateral and bilateral grade 3 microtia. Both patients had satisfactory aesthetic results. This technique allows for increased precision, may decrease operative time, and has good cosmetic outcomes.
Metanephric adenoma in a young female: a rare case report from Nepal
Authors: Yadav Deepak Kumar , Adhikari Mahesh Bahadur , Maharjan Bipin , Mishra Prashant , Basnet Birodh
Published: June 2023

Introduction:

Metanephric adenomas (MAs) of the kidney are rare benign epithelial lesions in the kidney that have been described in the literature, mainly through case reports, representing ~0.2% of renal masses. No prior case reports have been published from Nepal. We report one such case with MA presented to our center.

Case presentation:

A 25-year-old lady presented with complaints of recurrent hematuria for the past 6 months. Ultrasound of the abdomen revealed left gross hydronephrosis and reduced left renal parenchyma. A contrast-enhanced computerized scan of the abdomen and pelvis showed a heterogeneously enhancing soft tissue density lesion 65 mm×57 mm at the left renal pelvis extending into mid calyx and distally to proximal ureter, ~34 mm distal to pelviureteric junction causing moderate hydronephrosis, likely urothelial cell carcinoma. Urine cytology was negative for malignancy. Laparoscopic left nephroureterectomy with bladder cuff excision lymphadenectomy was done. The histopathology report came out to be consistent with MA and the lymph nodes were negative for malignancy. Immunohistochemistry study showed that the cells were positive for PAX8. During follow-up, she did not have hematuria and her postoperative period was uneventful.

Discussion:

From this report, we want to highlight the need to consider MA as a differential diagnosis of renal mass and differentiate MA from upper tract urothelial carcinoma, renal cell carcinoma, Wilms tumor, and papillary adenomas.

Conclusion:

MA is a rare renal lesion that may present as upper tract urothelial carcinoma. MA should be evaluated through histology and immunohistochemistry studies.
Clinical specificity profile for novel rapid acting antidepressant drugs
Authors: Scala Mauro , Fanelli Giuseppe , De Ronchi Diana , Serretti Alessandro , Fabbri Chiara
Published: June 2023

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants are not effective in all patients and often show a relevant response latency, with a range of adverse events, including weight gain and sexual dysfunction. Novel rapid agents were developed with the aim of overcoming at least in part these issues. Novel drugs target glutamate, gamma-aminobutyric acid, orexin, and other receptors, providing a broader range of pharmacodynamic mechanisms, that is, expected to increase the possibility of personalizing treatments on the individual clinical profile. These new drugs were developed with the aim of combining a rapid action, a tolerable profile, and higher effectiveness on specific symptoms, which were relatively poorly targeted by standard antidepressants, such as anhedonia and response to reward, suicidal ideation/behaviours, insomnia, cognitive deficits, and irritability. This review discusses the clinical specificity profile of new antidepressants, namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), and zuranolone (SAGE-217). The main aim is to provide an overview of the efficacy/tolerability of these compounds in patients with mood disorders having different symptom/comorbidity patterns, to help clinicians in the optimization of the risk/benefit ratio when prescribing these drugs.
Evaluation of distinct molecular architectures and coordinated regulation of the catabolic pathways of oestrogenic dioctyl phthalate isomers in Gordonia sp.
Authors: Dhar Rinita , Basu Suman , Bhattacharyya Mousumi , Dutta Tapan K.
Published: June 2023

Graphical Abstract

Biochemical and molecular analyses to reveal the regulation of catabolic pathways in the complete degradation of dioctyl phthalate isomers in

Gordonia

sp.
Evolution of cyclic di-GMP signalling on a short and long term time scale
Authors: Römling Ute , Cao Lian-Ying , Bai Feng-Wu
Published: June 2023

Graphical Abstract
Development of an extraction-free LAMP method for the generic detection of Orthopoxvirus and for the specific detection of Mpox virus
Authors: Li Zhiru , Sinha Amit , Zhang Yinhua , Tanner Nathan , Cheng Hui-Ting , Premsrirut Prem , Carlow Clotilde K. S.
Published: June 2023

Mpox is a neglected zoonotic disease endemic in West and Central Africa. The 2022 Mpox outbreak with more than 18,000 cases worldwide generated great concern about future outbreaks and highlighted the need for a simple and rapid diagnostic test. The Mpox virus, MPXV, is a member of the Orthopoxvirus genus that also contains other pathogenic viruses including variola virus, vaccinia virus, camelpox virus, and cowpox virus. Phylogenomic analysis of all available Orthopoxvirus genomes identified 10 distinct phylogroups, with isolates from infected humans distributed across various phylogroups interspersed with isolates from animal sources, indicating the zoonotic potential of these viruses. In this study, we developed a simple and sensitive colorimetric pan-Orthopoxvirus LAMP assay for broader Orthopoxvirus detection. We also developed an MPXV-specific probe that differentiates MPXV from other Orthopoxviruses on the N1R gene which differs by only a few nucleotides. In addition, we described an extraction-free protocol for use directly with swab eluates in LAMP assays, thereby eliminating the time and resources needed to extract DNA from the sample. Our direct LAMP assays are well-suited for low-resource settings and provide a valuable tool for rapid and scalable diagnosis and surveillance of Orthopoxviruses and MPXV.
The use of text mining to obtain a historical overview of research on therapeutic drug monitoring
Authors: Matsuzaki Tetsuo , Mizoguchi Hiroyuki , Yamada Kiyofumi
Published: June 2023

Therapeutic drug monitoring (TDM) is a routine clinical practice used to individualize drug dosing and thereby maintain drug efficacy and minimize the consequences of overexposure. TDM is applied to many drug classes, including immunosuppressants, anticoagulants, antineoplastic agents, and antibiotics. Considerable efforts have been made to establish routine TDM practice for each drug. However, because TDM has been developed within the context of specific drugs, there is insufficient understanding of historical trends in TDM research itself.

In this study, we employed text mining approaches to explore trends in the TDM research field. We first performed a PubMed search to determine which drugs and drug classes have been extensively studied in the context of TDM. This investigation revealed that the most commonly studied drugs were warfarin and cyclosporine, followed by tacrolimus, heparin, and vancomycin. In terms of drug classes, most publications focused on antineoplastic agents, anticoagulants, immunosuppressants, and antibiotics. We next used a newly developed python-based module to obtain PubMed records of publications relevant to TDM, and then subjected them to text mining. Our analyses revealed how TDM research has evolved over the years.
Exploring Inequalities in Population Health: A Phenome-Wide Study Examining the Association between Education and 833 diseases in Denmark
Authors: Pallesen Anna Vera Jørring , Mierau Jochen , Mortensen Laust Hvas
Published: June 2023

Objective

The social processes that shape people’s environment and ways of living tend to create inequalities in health. Better education is often, but not always, associated with lower disease incidence and better prognosis through a multitude of different mechanisms. Most often, research in this area examine few diseases of interest, thereby creating an array of disjoint analyses that lack comparability. The objective of this study is to create a novel atlas covering 833 diseases illustrating the associated educational gradients across a wide spectrum of health outcomes.

Method

Longitudinal, register-based study conducted on all Danish residents aged 30 years and over (N=4,258,789) between 2012 and 2021. We applied a phenome-wide approach to assess associations between three ISCED-based educational levels (low, medium, high) and the incidence of 833 diseases defined by ICD-10 diagnostic codes. Age-standardized incidence rates were estimated using Poisson regression adjusted for sex and birth cohort.

Results

Educational inequalities were observed in virtually all diseases studied and were, thus, not limited to particular disease areas. We found incidence rates of the vast majority of diseases increased with higher educational level (N=569). For 77 diagnoses, we observed an inverse educational gradient. Lower educated individuals had, with few exceptions, the highest incidence rates for non-communicable and communicable diseases.

Conclusions

Our atlas provides a full and detailed representation of the association between education and disease incidence. It brings attention to all diseases – not only the most prevalent – and makes it possible to examine the role of education across the universe of diseases.
Prolonged grief during and beyond the pandemic: Factors associated with levels of grief in a four time-point longitudinal survey of people bereaved in the first year of the COVID-19 pandemic
Authors: Harrop Emily , Mirra Renata Medeiros , Goss Silvia , Longo Mirella , Byrne Anthony , Farnell Damian JJ , Seddon Kathy , Penny Alison , Machin Linda , Sivell Stephanie , Selman Lucy E
Published: June 2023

Background

The COVID-19 pandemic has been a devastating and enduring mass-bereavement event, with uniquely difficult sets of circumstances experienced by people bereaved at this time. However, little is known about the long-term consequences of these experiences, including the prevalence of Prolonged Grief Disorder (PGD) and other conditions in pandemic-bereaved populations.

Methods

A longitudinal survey of people bereaved in the UK between 16 March 2020 and 2 January 2021, with data collected at baseline (n=711), c. 8 (n=383), 13 (n=295) and 25 (n=185) months post- bereavement. Using measures of Prolonged Grief Disorder (PGD) (Traumatic Grief Inventory), grief vulnerability (Adult Attitude to Grief Scale), and social support (Inventory of Social Support), this analysis examines how participant characteristics, characteristics of the deceased and pandemic- related circumstances (e.g. restricted visiting, social isolation, social support) are associated with grief outcomes, with a focus on levels of PGD.

Results

At baseline, 628 (88.6%) of participants were female, with a mean age of 49.5 (SD 12.9). 311 (43.8%) deaths were from confirmed/suspected COVID-19. Sample demographics were relatively stable across time points 34.6% of participants met the cut-off for indicated PGD at c. 13 months bereaved and 28.6% at final follow-up. Social isolation and loneliness in early bereavement and lack of social support over time strongly contributed to higher levels of PGD, whilst feeling well supported by healthcare professionals following the death was associated with reduced levels of PGD. Characteristics of the deceased most strongly associated with lower PGD scores, were a more distant relationship (e.g. death of a grandparent), an expected death and death occurring in a care- home. Participant characteristics associated with higher levels of PGD included low level of formal education and existence of medical conditions.

Conclusion

Results suggest higher than expected levels of PGD compared with pre-pandemic times, with important implications for bereavement policy, provision and practice now (e.g. strengthening of social and specialist support) and in preparedness for future pandemics and mass-bereavement events (e.g. guidance on infection control measures and rapid support responses).
Public Perceptions and Discussions of Premium Cigars on Reddit
Authors: Xie Zidian , Lee Sarah , Xu Emily , Li Dongmei
Published: June 2023

Introduction

While premium cigars have similar addictive, toxic, and carcinogenic constituents as other cigars and cigarettes, about 1% of the US adults reported premium cigar use from 2010 to 2019. This study aimed to understand public perceptions and discussions of premium cigars on Reddit, one of the most popular social media platforms.

Methods

Using keywords such as “premium cigar”, we extracted 2,238 Reddit posts from Reddit Archive between July 2019 and June 2021. Among them, 1,626 posts were related to premium cigars. By employing the inductive approach, we manually coded each Reddit post on premium cigars to understand public perceptions and discussions of premium cigars by summarizing them into different topics and subtopics.

Results

Longitudinal analysis showed that the number of Reddit posts on premium cigars increased since June 2020. Content analysis showed that among Reddit posts related to premium cigars, the most popular topic is “Information sharing” (75.72%), in which Reddit users shared their perceptions about premium cigars, asked for advice, and provided some recommendations about premium cigars. Over one-quarter of posts (27.17%) are sharing user experiences of premium cigars (such as taste). Nearly one-fifth (18.99%) of posts are discussing the affordability of premium cigars. In addition, 7.87% of posts are discussing legal/policy issues related to premium cigars, and 6.82% of posts are related to the health risks of premium cigars compared to cigarettes.

Conclusions

Public perceptions including misperceptions, user experiences, and affordability related to premium cigars have been actively discussed on Reddit.

Implications

With the increasing trend of premium cigar use, it is necessary to understand how premium cigars are perceived by the public and why they are becoming more popular. This study provides the first evidence on public perceptions and discussions of premium cigars on social media, which could provide useful information on future regulatory policies that aim to prevent the prevalence of premium cigars to protect public health.
The DCM Project Portal: A direct-to-participant platform of The DCM Research Project
Authors: Jordan Elizabeth S. , Grover Phoenix L. , Lin Jay , Starkey Carl A. , Finley Elizabeth A. , Ni Hanyu , Hershberger Ray E.
Published: June 2023

Study Objective

To develop a digital platform to conduct family-based, dilated cardiomyopathy (DCM) genetic research.

Design

Innovative approaches are needed to achieve large family enrollment targets. The DCM Project Portal, a direct-to-participant electronic recruitment, consent, and communication tool, was designed using prior experience with traditional enrollment methods, characteristics and feedback of current participants, and internet access of the US population.

Participants

DCM patients (probands) and their family members.

Results

The portal was designed as a self-guided, three module (registration, eligibility, and consent) process with internally created supporting informational and messaging resources integrated throughout. The experience can be tailored to user type and the format adapted with programmatic growth. Characteristics of participants of the recently completed DCM Precision Medicine Study were assessed as an exemplary user population. A majority of the diverse (34% non-Hispanic Black (NHE-B), 9.1% Hispanic; 53.6% female) proband (n=1223) and family members (n=1781) participants aged>18 years reportednot at allorrarelyhaving problems learning about their health from written information (81%) and a high confidence in completing medical forms (77.2%very muchoroftenconfident). A majority of participants across age and race-ethnicity groups reported internet access, with highest rates of no reported access in those>77 years, NHE-B, and Hispanic, which reflects patterns similar to rates reported by the US Census Bureau as of 2021.

Conclusions

Digital enrollment tools offer opportunity to improve access and efficiency. The portal is an example of a digital approach to family-based genetic research.
Factors predicting the visual outcome of intracorneal ring segment for keratoconus
Authors: Khanthik Apisit , Yaisawang Sasi , Puangsricharern Vilavun , Reinprayoon Usanee , Satitpitakul Vannarut , Kasetsuwan Ngamjit
Published: June 2023

Objectives

To find predictive factors and to construct predictive models using epidemiological and clinical preoperative factors for the visual acuity change after intracorneal ring segment (ICRS) implantation in keratoconus patients.

Methods

Medical records of 287 keratoconic eyes implanted with ICRS at Chula Refractive Surgery Centre of a tertiary university hospital (Bangkok, Thailand) between January 2012 and March 2022 were retrospectively reviewed for epidemiological and clinical preoperative variables, including those derived from Scheimpflug tomography. The correlation between these variables and postoperative uncorrected and corrected distance visual acuity change (ΔUDVA and ΔCDVA; logMAR scale) at 6 months was explored. Two hundred forty eight eyes (excluding cases with unmeasurable refraction) were randomized into 2 groups: the equation group (198 eyes) and the validation group (50 eyes). Multiple linear regression analysis was used to develop the predictive model from the equation group.

Results

Twenty preoperative variables were statistically correlated with ΔCDVA. Only the preoperative corrected distance visual acuity (CDVAp) strongly correlated with ΔCDVA (R = - 0.746). ΔUDVA correlated with only preoperative visual acuity, corneal astigmatism, and maximum Ambrósio relational thickness (ARTmax). CDVAp, spherical power (SPH), and anterior minimum sagittal curvature (Rmin) were the best predictors of ΔCDVA. The proposed model, ΔCDVA = 0.589 - 0.713×CDVAp - 0.010×SPH - 0.082×Rmin, had an acceptable predictability (R2 = 53.4%). The prediction was correct in 82% of the eyes within 0.22 logMAR.

Conclusions

Potential predictive factors and models for ICRS-induced changes in visual acuity were proposed as adjunctive tools for clinicians. Such tools could be used for case selection and during counseling before ICRS implantation to maximize surgical outcomes.
Multivariable risk modelling and survival analysis with machine learning in SARS-CoV-2 infection
Authors: Ciarmiello Andrea , Tutino Francesca , Giovannini Elisabetta , Milano Amalia , Barattini Matteo , Yosifov Nikola , Calvi Debora , Setti Maurizio , Sivori Massimiliano , Sani Cinzia , Bastreri Andrea , Staffiere Raffaele , Stefanini Teseo , Artioli Stefania , Giovacchini Giampiero
Published: June 2023

Aim

We evaluated the performance of a machine learning model based on demographic variables, blood tests, pre-existing comorbidities, and CT-based radiomic features to predict critical outcome in patients with acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods

We retrospectively enrolled 694 SARS-CoV-2 positive patients. Clinical and demographic data were extracted from clinical records. Radiomic data were extracted from CT. Patients were randomized to the training (80%, n=556) or test (20%, n=138) dataset. The training set was used to define the association between severity of disease and comorbidities, laboratory tests, demographic and CT-based radiomic variables, and to implement a risk prediction model. Models were evaluated using the C statistic and Brier scores. The test set was used for external validation.

Results

Patients who died (n=157) were predominantly male (66%) over the age of 50 with (median [range] C-reactive protein (CRP)=5 [1, 37] mg/dL, lactate dehydrogenase (LDH)=494 [141, 3,631] U/I and D-dimer=6.006 [168, 152.015] ng/ml). Surviving patients (n=537) had (median [range]) CRP=3 [0, 27] mg/dL, LDH=484 [78, 3.745] U/I, and D-dimer=1.133 [96, 55.660]ng/ml. The strongest risk factors were D-dimer, age, and cardiovascular disease.

The model implemented using the variables identified by the LASSO Cox regression analysis classified 152 of the 157 (97%) non-survivors as high risk individuals (Odd ratio=54.2 [21.9, 134.4]). Median survival in this group (14 [12, 19] days) was not different from that observed in non-survivors (12 [10, 14] days).

Conclusions

A machine learning model based on combined data available on the first days of hospitalization (demographics, CT-radiomics, comorbidities, and blood biomarkers), can identify SARS-CoV-2 patients at risk of serious illness and death.
Single-cell characterization of peripheral blood mononuclear cells from vedolizumab-treated patients with Crohn's disease identifies response-associated differences among the plasmacytoid dendritic cell and classical monocyte populations.
Authors: Li Yim Andrew Y.F. , Hageman Ishtu L. , Joustra Vincent W. , Elfiky Ahmed M.I.M. , Ghiboub Mohammed , Levin Evgeni , Verhoeff Jan , Verseijden Caroline , Admiraal-van den Berg Iris , Mannens Marcel M.A.M. , Jakobs Marja E. , Kenter Susan B. , Adams Alex T. , Satsangi Jack , D'Haens Geert R. , de Jonge Wouter J. , Henneman Peter
Published: June 2023

Vedolizumab (VDZ) is a monoclonal antibody approved for the treatment of Crohn's disease (CD). Despite its efficacy, non-response to VDZ is common in clinical practice with no clear understanding of how it manifests. Here, we characterized the cellular repertoire of responders and non-responders to VDZ during treatment. Peripheral blood mononuclear cells (PBMCs) were isolated from CD patients on VDZ treatment that were either steroid-free responder (N = 4) or non-responder (N = 4). Response was defined as ≥3 drop in Simple Endoscopic Score for Crohn's Disease (SES-CD) in combination with a ≥50% reduction in C-reactive protein (CRP) and fecal calprotectin and/or a ≥3 point drop in Harvey-Bradshaw Index (HBI). Single-cell repertoires were characterized using single-cell RNA-sequencing (scRNAseq) and mass cytometry by time of flight (CyTOF). Non-responders to VDZ presented more T cells, but fewer myeloid cells. T cells from non-responders presented lower expression of NFкB signaling inhibitors. A lower relative abundance of plasmacytoid dendritic cells (pDCs) was observed among non-responders. Moreover, non-responder-derived classical monocytes presented lower expression of genes involved in wound-healing and cytokine-cytokine receptor signaling. Taken together, non-response to VDZ during treatment is associated with differences in abundance and expression among T and myeloid cells.
Refining the impact of genetic evidence on clinical success
Authors: Minikel Eric Vallabh , Painter Jeffery L , Dong Coco Chengliang , Nelson Matthew R.
Published: June 2023

The cost of drug discovery and development is driven primarily by failure, with just ∼10% of clinical programs eventually receiving approval. We previously estimated that human genetic evidence doubles the success rate from clinical development to approval. In this study we leverage the growth in genetic evidence over the past decade to better understand the characteristics that distinguish clinical success and failure. We estimate the probability of success for drug mechanisms with genetic support is 2.6 times greater than those without. This relative success varies among therapy areas and development phases, and improves with increasing confidence in the causal gene, but is largely unaffected by genetic effect size, minor allele frequency, or year of discovery. These results suggest we are far from reaching peak genetic insights to aid the discovery of targets for more effective drugs.
Patient characteristics associated with clinically coded long COVID: an OpenSAFELY study using electronic health records
Authors: Wei Yinghui , Horne Elsie MF , Knight Rochelle , Cezard Genevieve , Walker Alex , Fisher Louis , Denholm Rachel , Taylor Kurt , Walker Venexia , Riley Stephanie , Williams Dylan M , Willans Robert , Davy Simon , Bacon Sebastian , Goldacre Ben , Mehrkar Amir , Denaxas Spiros , Greaves Felix , Silverwood Richard J , Sheikh Aziz , Chaturvedi Nish , Wood Angela M , Macleod John , Steves Claire , Sterne Jonathan AC
Published: June 2023

Despite reports of post-COVID-19 syndromes (long COVID) are rising, clinically coded long COVID cases are incomplete in electronic health records. It is unclear how patient characteristics may be associated with clinically coded long COVID. With the approval of NHS England, we undertook a cohort study using electronic health records within the OpenSAFELY-TPP platform in England, to study patient characteristics associated with clinically coded long COVID from 29 January 2020 to 31 March 2022. We estimated age-sex adjusted hazard ratios and fully adjusted hazard ratios for coded long COVID. Patient characteristics included demographic factors, and health behavioural and clinical factors. Among 17,986,419 adults, 36,886 (0.21%) were clinically coded with long COVID. Patient characteristics associated with coded long COVID included female sex, younger age (under 60 years), obesity, living in less deprived areas, ever smoking, greater consultation frequency, and history of diagnosed asthma, mental health conditions, pre-pandemic post-viral fatigue, or psoriasis. The strength of these associations was attenuated following two-dose vaccination compared to before vaccination. The incidence of coded long COVID was higher after hospitalised than non-hospitalised COVID-19. These results should be interpreted with caution given that long COVID was likely under-recorded in electronic health records.
Type 2 diabetes and fracture risk: deciphering the complex relationship with both genetic and observational evidence
Authors: Zhao Pianpian , Sheng Zhifeng , Xu Lin , Li Peng , Xiao Wenjin , Yuan Chengda , Xu Zhanwei , Yang Mengyuan , Qian Yu , Zhong Jiadong , Gu Jiaxuan , Karasik David , Zheng Hou-Feng
Published: June 2023

The “diabetic bone paradox” suggested that type 2 diabetes (T2D) patients would have higher areal bone mineral density (BMD) but higher fracture risk than individuals without T2D. In this study, we found that the genetically predicted T2D was associated with higher BMD and lower risk of fracture in both wGRS and two-sample MR analyses. We also identified ten genomic loci shared between T2D and fracture, with the top signal at SNP rs4580892 in the intron of geneRSPO3. And the higher expression in adipose subcutaneous and higher protein level in plasma ofRSPO3were associated with increased risk of T2D, but decreased risk of fracture. In the prospective study, T2D was observed to be associated with higher risk of fracture, but BMI mediated 30.2% of the protective effect. However, when stratified by the risk factors secondary to the disease, we observed that the effect of T2D on the risk of fracture decreased when the number of risk factors secondary to T2D decreased, and the association became non-significant if the T2D patients carried none of the risk factors. In conclusion, the genetically determined T2D might not be associated with higher risk of fracture. And the shared genetic architecture between T2D and fracture suggested a top signal aroundRSPO3gene. The observed effect size of T2D on fracture risk decreased if the risk factors secondary to T2D could be eliminated. Therefore, it is important to manage the complications of T2D to prevent the risk of fracture.
Simultaneous detection and quantification of multiple pathogen targets in wastewater
Authors: Rao Gouthami , Capone Drew , Zhu Kevin , Knoble Abigail , Linden Yarrow , Clark Ryan , Lai Amanda , Kim Juhee , Huang Ching-Hua , Bivins Aaron , Brown Joe
Published: June 2023

Wastewater-based epidemiology has emerged as a critical tool for public health surveillance, building on decades of environmental surveillance work for pathogens such as poliovirus. Work to date has been limited to monitoring a single pathogen or small numbers of pathogens in targeted studies; however, few studies consider simultaneous quantitative analysis of a wide variety of pathogens, which could greatly increase the utility of wastewater surveillance. We developed a novel quantitative multi-pathogen surveillance approach (35 pathogen targets including bacteria, viruses, protozoa, and helminths) using TaqMan Array Cards (TAC) and applied the method on concentrated wastewater samples collected at four wastewater treatment plants in Atlanta, GA from February to October of 2020. From sewersheds serving approximately 2 million people, we detected a wide range of targets including many we expected to find in wastewater (e.g., enterotoxigenicE. coliandGiardiain 97% of 29 samples at stable concentrations) as well as unexpected targets includingStrongyloides stercoralis(a human threadworm rarely observed in the USA). Other notable detections included SARS-CoV-2, but also several pathogen targets that are not commonly included in wastewater surveillance likeAcanthamoebaspp.,Balantidium coli,Entamoeba histolytica, astrovirus, norovirus, and sapovirus. Our data suggest broad utility in expanding the scope of enteric pathogen surveillance in wastewaters, with potential for application in a variety of settings where pathogen quantification in fecal waste streams can inform public health surveillance and selection of control measures to limit infections.