bluuebunny/crossref_metadata_2025 huggingface dataset:
Inquiry into faith-based social reintegration programs for recovering drug addicts in Nigeria
Authors: Olajire Oluyinka Olutola , Oyekola Isaac Akintoyese
Published: May 2022

Purpose

The purpose of this study is to subject faith-based organizations (FBOs)-operated social reintegration programs for recovering drug addicts to scrutiny to understand their effectiveness in addressing the three-pillar social needs.

Design/methodology/approach

Using concurrent mixed methods research design, a sample size of 156 respondents, 15 in-depth interviewees and 12 key informants was selected purposely from three FBOs and three National Drug Law Enforcement Agency (NDLEA) State Command Areas in Nigeria. Data were collected using questionnaire survey, interviews, observation and document review, and then analyzed using descriptive and content analyses.

Findings

Findings showed nine different noncore social reintegration programs for recovering drug-addicts with different required rates of participation and diverse purposes. Also, the results showed that the three-pillar social needs of recovering drug addicts for successful reintegration into the society were not provided for by the FBOs. Finally, findings showed that majority of the respondents were only slightly satisfied with the overall services rendered at the selected FBOs, and these services were not properly monitored by relevant government agency.

Social implications

Appropriate regulations that will check and balance the activities of treatment providers involved in social reintegration is recommended to achieve optimal level of physical, psychological and social health for recovering drug addicts.

Originality/value

To the best of the authors’ knowledge ,this is a pioneer study that investigated faith-based social reintegration programs for recovering drug addicts in Nigeria.
Patient perceptions of psoriatic disease in Japan: Results from the Japanese subgroup of the Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey
Authors: Torii Hideshi , Kishimoto Mitsumasa , Tanaka Masayuki , Noguchi Hidehisa , Chaudhari Siddharth
Published: May 2022

The population‐based Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey was designed to better understand patient and dermatologist perceptions of the disease burden of psoriasis (PsO) and their treatment expectations. UPLIFT was a cross‐sectional, quantitative, online survey conducted in Europe, North America, and Japan between 2 March and 3 June 2020. In Japan, 391 patients reporting a diagnosis of PsO and/or psoriatic arthritis (PsA) were surveyed (75% had PsO alone, 23% had PsO and PsA, and 2% had PsA alone). Self‐reported body surface area (BSA) data were available for 309 Japanese patients, with the majority (80%) reporting PsO‐involved BSA ≤3 palms. Current symptoms of PsO were rated as moderate or severe by 43% of Japanese patients with BSA ≤3 palms, and severe by 44% of patients with BSA 4–10 palms. PsO frequently occurred in ≥1 special areas, most commonly the scalp in 76% of Japanese patients with BSA ≤3 palms, and ≥90% of those with BSA ≥4 palms. Furthermore, musculoskeletal symptoms in 42% of patients with PsO alone were suggestive of PsA. Whereas Japanese patients with BSA ≤3 palms mainly reported receiving topical therapy alone (34%) or no treatment (32%), 64% patients with BSA 4–10 palms reported receiving systemic therapy. Overall, 21% of Japanese patients with self‐perceived mild symptoms of PsO and 48% of patients with special area involvement experienced at least a moderate impact of disease on quality of life (Dermatology Life Quality Index score >5). Moreover, patients and dermatologists differed in their perceptions of determinants of PsO severity and treatment, and office visit discussions. In general, these findings from the Japanese subgroup of the UPLIFT survey demonstrated that a high proportion of patients perceived their symptoms to be moderate or severe irrespective of the level of skin involvement, suggesting a persistent unmet treatment need.
Therapeutic outcomes and prognostic factors in patients with hypertrophic herpes simplex infection treated with imiquimod: A systematic review and meta‐analysis of individual patient data from case reports and case series
Authors: Leeyaphan Charussri , Nanchaipruek Yanisorn , Phinyo Phichayut
Published: May 2022

Hypertrophic herpes simplex (HHS) often has atypical presentations, such as a hypertrophic mass or ulcers, with chronic courses. This situation poses a diagnostic challenge and results in delayed treatment. Imiquimod was used as a treatment for HHS by several studies, but the therapeutic outcomes varied. This systematic review and meta‐analysis of individual patient data was conducted to investigate the therapeutic outcomes and prognostic factors of imiquimod treatment for patients with HHS. Biomedical databases (Embase, PubMed, Medline, Cochrane Controlled Trials Register, and ClinicalTrials.gov) were searched for all types of clinical studies reporting the complete cure rate and the time to complete response to imiquimod therapy between 1926 and 2021. Quantitative analysis of individual patient data was performed using multivariable flexible parametric survival regression with cluster variance correction. A total of 12 019 articles were identified and screened for eligibility. Twenty‐five studies (21 case reports and four case series) with a combined total of 42 patients were included. The complete cure rate for imiquimod treatment was estimated at 88.1%. The median time to complete response was 60 days (95% confidence interval 35–70). Combined treatment, male sex, and an age less than 50 years were identified as significant prognostic factors for a shorter time to complete cure. A severe local reaction was reported in 2.3%. Imiquimod therapy has high effectiveness and safety in curing HHS. Patients who were male or younger than 50 years or whose treatments were combined with thymidine kinase‐dependent antivirals had the best prognoses and were more likely to respond to treatment.
Graminoids vary in functional traits, carbon dioxide and methane fluxes in a restored peatland: Implications for modelling carbon storage
Authors: Goud Ellie M. , Touchette Sabrina , Strachan Ian B. , Strack Maria
Published: May 2022

One metric of peatland restoration success is the re‐establishment of a carbon sink, yet considerable uncertainty remains around the time‐scale of carbon sink trajectories. Conditions post‐restoration may promote the establishment of vascular plants such as graminoids, often at greater density than would be found in undisturbed peatlands, with consequences for carbon storage. Although graminoid species are often considered as a single plant functional type (PFT) in land‐atmosphere models, our understanding of functional variation among graminoid species is limited, particularly in a restoration context.

We used a traits‐based approach to evaluate graminoid functional variation and to assess whether different graminoid species should be considered a single PFT or multiple types. We tested hypotheses that greenhouse gas fluxes (CO2, CH4) would vary due to differences in plant traits among five graminoid species in a restored peatland in central Alberta, Canada. We further hypothesized that species would form two functionally distinct groupings based on taxonomy (grass, sedge).

Differences in gas fluxes among species primarily reflected variation in leaf physiology related to photosynthetic efficiency and resource‐use, and secondarily by plant size. Multivariate analyses did not reveal distinct functional groupings based on taxonomy or environmental preferences. Rather, we identified functional groups defined by plant traits and carbon fluxes that are consistent with ecological strategies related to differences in growth rate, resource‐acquisition and leaf economics, representing plants with either a strategy to grow quickly and invest in resource capture or to prioritize structural investment and resource conservation. These functional groups displayed larger average carbon fluxes compared to graminoid PFTs currently used in modelling.

Synthesis. Existing PFT designations in peatland models may be more appropriate for pristine or high‐latitude systems than those under restoration. Although replacing PFTs with plant traits remains a challenge in peatlands, traits related to leaf physiology and growth rate strategies offer a promising avenue for future applications.
Predictors of progression in rheumatoid arthritis‐associated interstitial lung disease: A single‐center retrospective study from China
Authors: Liu Lei , Fang Chunxiao , Sun Bo , Bao Ruyi , Zhang Hongfeng
Published: May 2022

Aim

Interstitial lung disease (ILD) is a common extra‐articular manifestation of rheumatoid arthritis (RA) and is associated with high mortality, especially in progressive ILD. We aimed to identify predictors of disease progression in the early stages of ILD in a large sample of patients with RA.

Method

The medical records of 201 RA‐ILD patients were retrospectively analyzed. According to changes in their pulmonary function tests, patients were divided into progressive disease and stable disease groups. Data were collected on clinical characteristics, laboratory findings, chest high‐resolution computed tomography, and therapeutic agents. Univariate and multivariate analyses were performed to identify predictors of ILD progression.

Results

During a median follow up of 38 months, 105 (52.5%) patients were diagnosed with progressive ILD. These patients were mostly male, past or present smokers (P = 0.028, P = 0.021, respectively). Higher Health Assessment Questionnaire‐Disability Index score and higher Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28‐ESR) were observed in the ILD progression group (P = 0.003, P < 0.001, respectively). There were no significant differences in baseline respiratory symptoms, pulmonary function, or laboratory features. Multivariate analysis indicated that high DAS28‐ESR, definite usual interstitial pneumonia pattern, fibrosis score, and less use of cyclophosphamide were independent risk factors for RA‐ILD progression. Fifteen (7.46%) patients died during the follow up, and the most frequent cause of death was lung infection.

Conclusion

Our results suggested that high disease activity, definite usual interstitial pneumonia pattern, fibrosis score, and less use of cyclophosphamide at the onset of ILD may indicate the progression of ILD in RA patients.
Epidermal growth factor receptor tyrosine kinase inhibitors for de novo T790M mutation: A retrospective study of 44 patients
Authors: Chang John Wen‐Cheng , Huang Chen‐Yang , Fang Yueh‐Fu , Chang Ching‐Fu , Yang Cheng‐Ta , Kuo Chih‐Hsi Scott , Hsu Ping‐Chih , Wu Chiao‐En
Published: May 2022

Background

This study aimed to evaluate possible treatment strategies for patients with de novo T790M mutation‐positive (T790M+) non‐small‐cell lung cancer (NSCLC).

Methods

Patients diagnosed with de novo T790M+ NSCLC and treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) between 2011 and 2018 at a regional hospital in Taiwan were retrospectively reviewed. Their clinicopathological characteristics and subsequent treatment information were collected, and potential prognostic factors were identified using univariate and multivariate analyses.

Results

All tumors with T790M mutations coexisted with sensitizing mutations. Through the last follow‐up in May 2021, afatinib and osimertinib demonstrated better progression‐free survival (PFS, p < 0.01) and overall survival (OS, p < 0.01) than gefitinib and erlotinib. Additionally, patients with low T790M ratios had better PFS than those with high T790M ratios, implying that the proportion of T790M+ tumors determined the response to EGFR‐TKIs. Multivariate analysis confirmed that both EGFR‐TKI treatment (osimertinib hazard ratio [HR] 0.06, 95% confidence interval [CI] 0.01–0.30; afatinib HR 0.09, 95% CI 0.02–0.39) and a low T790M ratio (HR 0.29, 95% CI 0.12–0.69) were independently favorable prognostic factors for patients with de novo T790M+ NSCLC. Median PFS was 6.1 (95% CI 4.4–7.8) months. In addition, patients treated with first‐generation (1G)/second‐generation (2G) EGFR‐TKIs followed by osimertinib (n = 8) demonstrated the best OS compared with patients treated with frontline osimertinib (n = 5) or 1G/2G EGFR‐TKIs without osimertinib (n = 28, p < 0.01).

Conclusion

Sequential TKIs may represent an alternative option for de novo T790M mutation, particularly frontline afatinib and tumors with low T790M ratios.
Walking the Talk? Managing Errors in the Audit Profession*
Authors: Gold Anna , Detzen Dominic , van Mourik Oscar , Wallage Philip , Wright Arnold
Published: May 2022

Errors reflect unintended deviations from plans or goals and commonly carry negative connotations. Although errors cannot be eliminated, they offer opportunities for learning and innovation. Audit firms employ powerful mechanisms, such as review processes, to prevent or detect audit errors and safeguard their work in the public interest. At the same time, the profession recognizes positive long‐term outcomes of errors in terms of continuous learning to enhance auditor skills and, ultimately, audit quality. The current study employs semistructured interviews with Dutch auditors to investigate how they manage the tensions emanating from extant public and regulatory demands for flawless audits while embracing errors as opportunities for learning. Our findings reveal that auditors express a positive attitude toward openly communicating audit errors, but, in substance, they espouse negative emotions and defensive strategies for fear of repercussions. We argue that the excessive emphasis audit firms and oversight bodies place on error prevention conditions auditors into perceiving errors as negative and avoidable events. We assert these attitudes result from the profession's efforts to maintain status and legitimacy in the eyes of the public and the regulator, where any auditor error may shed doubt on auditors' work in the public interest. In sum, our findings indicate that viewing errors as incompatible with audit work makes the profession susceptible not only to repeating errors but also to missing out on opportunities to improve services and to achieve innovation.
Aphid‐parasitoids trophic relationship in a cereal crop succession system: Population oscillation and food webs
Authors: dos Santos Carlos Diego Ribeiro , Lau Douglas , Redaelli Luiza Rodrigues , Jahnke Simone Mundstock , Pereira Paulo Roberto Valle da Silva , Engel Eduardo , Sampaio Marcus Vinicius
Published: May 2022

In the 1970s, cereal aphids populations (specially Metopolophium dirhodum) were out of balance in the subtropical region of South America and a successful biological control program with the introduction of parasitoids restored equilibrium. After that, changes in crop systems may have affected aphid‐parasitoid communities.

The objective of this work was to evaluate the current assemblage of cereal aphid parasitoids, describing their oscillations, parasitism level, and trophic relationships in food webs in a cereal succession system (wheat‐corn‐oat) currently adopted in this region.

Over a year, the associated parasitoid/hyperparasitoid species were inventoried by field‐exposed Rhopalosiphum padi, Schizaphis graminum, M. dirhodum, and Sitobion avenae (recruitment method) and by Moericke traps.

Six species of primary parasitoids were sampled in both aphids and traps with the same abundance sequence: A. platensis, A. rhopalosiphi, L. testaceipes, D. rapae, A. uzbekistanicus, and A. ervi.

Parasitism and complexity of food webs were higher during the wheat season (winter–spring), decreasing in corn (summer) and increasing again in oat (autumn).

In the current assemblage of cereal aphid parasitoids in the subtropical region of South America, three species of parasitoids that were already present before the biological control program and three that were introduced oscillate in abundance throughout the year, resulting in an alternation of the complexity of the food webs and in the levels of parasitism in the crop seasons. A. platensis and A. rhopalosiphi are the most abundant species and A. rhopalosiphi remains fundamental in the control of M. dirhodum and S. avenae.
Systemic hormonal contraception and risk of venous thromboembolism
Authors: Heikinheimo Oskari , Toffol Elena , Partonen Timo , But Anna , Latvala Antti , Haukka Jari
Published: May 2022

Introduction

The increased risk of venous thromboembolism associated with the use of hormonal contraception is well recognized, but evidence regarding hormonal contraception containing natural estradiol is limited. This study aimed to assess the associations between the patterns of use of different systemic hormonal contraceptives and the risk of venous thromboembolism during 2017–2019.

Material and Methods

All fertile‐aged women (15–49 years) living in Finland in 2017 and using hormonal contraception in 2017 and their 1:1 age‐ and residence‐matched controls not using hormonal contraception in 2017 (altogether 587 559 women) were selected from the Prescription Centre. All incident venous thromboembolism cases during 2018–2019 and their 4:1 age‐matched controls were further analyzed in a prospective nested case–control design to assess the associations between the use (starting, stopping, continuous vs no use) of different hormonal contraception types and venous thromboembolism.

Results

Altogether, 1334 venous thromboembolism cases occurred during the follow‐up period (incidence rate 1.14 per 1000 person‐years, 95% confidence interval [CI] 1.08–1.20), with an incidence rate ratio of hormonal contraception vs no hormonal contraception use of 1.42 (95% CI 1.27–1.58). Compared with non‐use, starting the use of gestodene and ethinylestradiol (adjusted odds ratio [aOR] 2.85; 95% CI 1.62–5.03), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 0.98–2.44), desogestrel and ethinylestradiol (aOR 1.97; 95% CI 0.99–3.92), and transdermal patch releasing norelgestromin and ethinylestradiol (aOR 5.10; 95% CI 1.12–23.16), as well as continuing the use of gestodene and ethinylestradiol (aOR 2.60; 95% CI 1.61–4.21), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 1.02–2.37), cyproterone‐acetate and estrogen/ethinylestradiol (aOR 1.66; 95% CI 1.06–2.61), and vaginal ring releasing etonogestrel and ethinylestradiol (aOR 3.27; 95% CI 1.95–5.48) were associated with venous thromboembolism risk. Regarding the type of estrogen, the highest risk was associated with current use (vs non use in the previous 180 days) of ethinylestradiol‐containing preparations (aOR 2.20; 95% CI 1.82–2.65), followed by estradiol‐containing preparations (aOR 1.39; 95% CI 1.04–1.87) with no risk for progestin‐only hormonal contraception. Current use of estradiol‐containing preparations was not associated with venous thromboembolism risk after exclusion of cyproterone‐acetate and estrogen/ethinylestradiol (aOR 1.05; 95% CI 0.66–1.66).

Conclusions

An increased risk of venous thromboembolism is associated with ethinylestradiol‐containing combined preparations. The use of estradiol‐containing combined preparations confers only a slightly increased risk, possibly driven by cyproterone‐containing combined oral contraceptives, whereas the use of progestin‐only contraception is not associated with venous thromboembolism.
Long‐term incidence of endometrial cancer after endometrial resection and ablation: A population based Swedish gynecologic cancer group (SweGCG) study
Authors: Flöter Rådestad Angelique , Dahm‐Kähler Pernilla , Holmberg Erik , Bjurberg Maria , Hellman Kristina , Högberg Thomas , Kjölhede Preben , Marcickiewicz Janusz , Rosenberg Per , Stålberg Karin , Åvall‐Lundqvist Elisabeth , Borgfeldt Christer
Published: May 2022

Introduction

Minimally invasive methods to reduce menorrhagia were introduced in the 1980s and 1990s. Transcervical endometrial resection (TCRE) and endometrial ablation (EA) are two of the most frequently used methods. As none of them can guarantee a complete removal of the endometrium, there are concerns that the remaining endometrium may develop to endometrial cancer (EC) later in life. The primary aim was to analyze the long‐term incidence of EC after TCRE and EA in a nationwide population. The secondary aim was to assess the two treatment modalities separately.

Material and Methods

The Swedish National Patient Registry and National Quality Registry for Gynecological Surgery were used for identification of women who had TCRE or EA performed between 1997–2017. The cohort was followed from the first TCRE or EA until hysterectomy, diagnosis of EC, or death. Follow‐up data were retrieved from the National Cancer Registry and the National Death Registry. Expected incidence for EC in Swedish women was calculated using Swedish data retrieved from the NORDCAN project after having taken into account differences of age and follow‐up time. Cumulative incidence of EC after TCRE and EA, was calculated. A standardized incidence ratio was calculated based on the expected and observed incidence, stratified by age and year of diagnosis.

Results

In total, 17 296 women (mean age 45.1 years) underwent TCRE (n = 8626) or EA (n = 8670). Excluded were 3121 who had a hysterectomy for benign causes during follow up. During a median follow‐up time of 7.1 years (interquartile range 3.1–13.3 years) the numbers of EC were 25 (0.3%) after TCRE and 2 (0.02%) after EA, respectively. The observed incidence was significantly lower than expected (population‐based estimate) after EA but not after TCRE, giving a standardized incidence ratio of 0.13 (95% confidence interval [CI] 0.03–0.53) after EA and 1.27 (95% CI 0.86–1.88) after TCRE. Median times to EC were 3.0 and 8.3 years after TCRE and EA, respectively.

Conclusions

There was a significant reduction of EC after EA, suggesting a protective effect, whereas endometrial resection showed an incidence within the expected rate.
Clinical and genetic findings in TRPM1‐related congenital stationary night blindness
Authors: Iosifidis Christos , Liu Jingshu , Gale Theodora , Ellingford Jamie M. , Campbell Christopher , Ingram Stuart , Chandler Kate , Parry Neil R. A. , Black Graeme C. , Sergouniotis Panagiotis I.
Published: May 2022

Purpose

Congenital stationary night blindness (CSNB) is a heterogeneous group of Mendelian retinal disorders that present in childhood. Biallelic variants altering the protein‐coding region of the TRPM1 gene are one of the commonest causes of CSNB. Here, we report the clinical and genetic findings in 10 unrelated individuals with TRPM1‐retinopathy.

Methods

Study subjects were recruited through a tertiary clinical ophthalmic genetic service at Manchester, UK. All participants underwent visual electrodiagnostic testing and panel‐based genetic analysis.

Results

Study subjects had a median age of 8 years (range: 3–20 years). All probands were myopic and had electroretinographic findings in keeping with complete CSNB. Notably, three probands reported no night vision problems. Fourteen different disease‐associated TRPM1 variants were detected. One individual was homozygous for the NM_001252024.2 (TRPM1):c.965 + 29G>A variant and a mini‐gene assay highlighted that this change results in mis‐splicing and premature protein termination. Additionally, two unrelated probands who had CSNB and mild neurodevelopmental abnormalities were found to carry a 15q13.3 microdeletion. This copy number variant encompasses seven genes, including TRPM1, and was encountered in the heterozygous state and in trans with a missense TRPM1 variant in each case.

Conclusion

Our findings highlight the importance of comprehensive genomic analysis, beyond the exons and protein‐coding regions of genes, for individuals with CSNB. When this characteristic retinal phenotype is accompanied by extraocular findings (including learning and/or behavioural difficulties), a 15q13.3 microdeletion should be suspected. Focused analysis (e.g. microarray testing) is recommended to look for large‐scale deletions encompassing TRPM1 in patients with CSNB and neurodevelopmental abnormalities.
Acute appendicitis in a patient immunised with COVID‐19 vaccine: A case report with morphological analysis
Authors: Marconi Ettore , Crescioli Giada , Bonaiuti Roberto , Pugliese Lavinia , Santi Raffaella , Nesi Gabriella , Cerbai Elisabetta , Vannacci Alfredo , Lombardi Niccolò
Published: May 2022

Although the benefit/risk profile for mRNA COVID‐19 vaccines is recognised as extremely favourable, appendicitis is currently considered an adverse event (AE) of special interest. We describe the case of a 58‐year‐old female who presented with signs and symptoms of appendicitis approximately 48 hours after her first injection of the Pfizer‐BioNTech vaccine. Abdominal ultrasound revealed fluid collection in the right iliac fossa and cecal wall thickening. Following the surgical visit, CT scan with contrast showed a distended appendix with thickened walls, suggestive of acute appendicitis. The patient tested negative to upper respiratory COVID‐19 reverse transcription‐polymerase chain reaction. Clinical trials and observational studies suggest a possible association between appendicitis and COVID‐19 vaccines. Th‐1 driven granulomatous inflammation reported in our case represents an infrequent nonspecific chronic inflammation of the appendix, especially in the setting of delayed or interval appendectomy. In view of the current paediatric vaccination campaign, we recommend monitoring the safety profile and potential gastrointestinal AEs associated with mRNA COVID‐19 vaccines to swiftly manage subjects with gastrointestinal symptoms and prevent potential complications.
Body shape and diet reflect arboreality degree of five congeneric snakes sympatric in the Atlantic forest
Authors: Banci Karina Rodrigues da Silva , Guimarães Murilo , Siqueira Lucas Henrique Carvalho , Muscat Edelcio , Sazima Ivan , Marques Otavio Augusto Vuolo
Published: May 2022

The substrate use by animals may influence both their morphology and diet. Species of the genus Chironius are among the most conspicuous frog‐eating, arboreal snakes in South America. The aim of the present study was to investigate whether diet and morphology relate to substrate use in five sympatric Chironius species from the Atlantic Forest. Our hypothesis is that habitat pressure is strong enough so that even closely related species will present differences. We collected morphological and diet data from specimens of C. bicarinatus, C. exoletus, C. foveatus, C. fuscus, and C. laevicollis housed in scientific collections. Information on habitat use were obtained by monitoring free‐ranging animals using thread‐bobbins and also from the literature. Our results demonstrate that C. foveatus is the most arboreal species, and C. laevicollis is the most terrestrial among the five studied species. Chironius foveatus is the slenderest, with one of the longest relative tail lengths, the narrowest ventral scales, the highest vertebral density, the largest eye diameter, green body color, and diet based on tree frogs (Hylidae). These traits indicate a higher arboreality for this species. On the other extreme, C. laevicollis is the stoutest species, and has the shortest tail, the largest head, the lowest vertebral density, and diet based on ground‐living frogs (Leptodactylidae). These traits indicate pronounced terrestriality for this species. The other three species have traits intermediate between the extremes showed by C. foveatus and C. laevicollis. We found evidence for a close relationship between arboreality or terrestriality, morphology, and diet.
Estrogen induces the expression of EBV lytic protein ZEBRA, a marker of poor prognosis in nasopharyngeal carcinoma
Authors: Dochi Hirotomo , Kondo Satoru , Murata Takayuki , Fukuyo Masaki , Nanbo Asuka , Wakae Kousho , Jiang Wen‐Ping , Hamabe‐Horiike Toshihide , Tanaka Mariko , Nishiuchi Takumi , Mizokami Harue , Moriyama‐Kita Makiko , Kobayashi Eiji , Hirai Nobuyuki , Komori Takeshi , Ueno Takayoshi , Nakanishi Yosuke , Hatano Miyako , Endo Kazuhira , Sugimoto Hisashi , Wakisaka Naohiro , Juang Shin‐Hun , Muramatsu Masamichi , Kaneda Atsushi , Yoshizaki Tomokazu
Published: May 2022

Several epidemiological studies have suggested that Epstein–Barr virus (EBV) lytic infection is essential for the development of nasopharyngeal carcinoma (NPC), as the elevation of antibody titers against EBV lytic proteins is a common feature of NPC. Although ZEBRA protein is a key trigger for the initiation of lytic infection, whether its expression affects the prognosis and pathogenesis of NPC remains unclear. In this study, 64 NPC biopsy specimens were analyzed using immunohistochemistry. We found that ZEBRA was significantly associated with a worsening of progression‐free survival in NPC (adjusted hazard ratio, 3.58; 95% confidence interval, 1.08–11.87; p = 0.037). Moreover, ZEBRA expression positively correlated with key endocrinological proteins, estrogen receptor α, and aromatase. The transcriptional level of ZEBRA is activated by estrogen in an estrogen receptor α‐dependent manner, resulting in an increase in structural gene expression levels and extracellular virus DNA copy number in NPC cell lines, reminiscent of lytic infection. Interestingly, it did not suppress cellular proliferation or increase apoptosis, in contrast with cells treated with 12‐O‐tetradecanoylphorbol‐13‐acetate and sodium butyrate, indicating that viral production induced by estrogen is not a cell lytic phenomenon. Our results suggest that intratumoral estrogen overproduced by aromatase could induce ZEBRA expression and EBV reactivation, contributing to the progression of NPC.
Analysis of microbiome in gastrointestinal stromal tumors: Looking for different players in tumorigenesis and novel therapeutic options
Authors: Ravegnini Gloria , Fosso Bruno , Ricci Riccardo , Gorini Francesca , Turroni Silvia , Serrano Cesar , Pilco‐Janeta Daniel F. , Zhang Qianqian , Zanotti Federica , De Robertis Mariangela , Nannini Margherita , Pantaleo Maria Abbondanza , Hrelia Patrizia , Angelini Sabrina
Published: May 2022

Preclinical forms of gastrointestinal stromal tumor (GIST), small asymptomatic lesions, called microGIST, are detected in approximately 30% of the general population. Gastrointestinal stromal tumor driver mutation can be already detected in microGISTs, even if they do not progress into malignant cancer; these mutations are necessary, but insufficient events to foster tumor progression. Here we profiled the tissue microbiota of 60 gastrointestinal specimens in three different patient cohorts—micro, low‐risk, and high‐risk or metastatic GIST—exploring the compositional structure, predicted function, and microbial networks, with the aim of providing a complete overview of microbial ecology in GIST and its preclinical form. Comparing microGISTs and GISTs, both weighted and unweighted UniFrac and Bray–Curtis dissimilarities showed significant community‐level separation between them and a pronounced difference in Proteobacteria, Firmicutes, and Bacteroidota was observed. Through the LEfSe tool, potential microbial biomarkers associated with a specific type of lesion were identified. In particular, GIST samples were significantly enriched in the phylum Proteobacteria compared to microGISTs. Several pathways involved in sugar metabolism were also highlighted in GISTs; this was expected as cancer usually displays high aerobic glycolysis in place of oxidative phosphorylation and rise of glucose flux to promote anabolic request. Our results highlight that specific differences do exist in the tissue microbiome community between GIST and benign lesions and that microbiome restructuration can drive the carcinogenesis process.
Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study
Authors: Yonemori Kan , Kuboki Yasutoshi , Hasegawa Kosei , Iwata Takashi , Kato Hidenori , Takehara Kazuhiro , Hirashima Yasuyuki , Kato Hisamori , Passey Chaitali , Buchbjerg Jeppe Klint , Harris Jeffrey R. , Andreassen Camilla Mondrup , Nicacio Leonardo , Soumaoro Ibrahima , Fujiwara Keiichi
Published: May 2022

New treatments, particularly second‐line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody–drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single‐arm, open‐label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non‐Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1–2 prior lines of therapy. In part 1, no dose‐limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment‐emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non‐Japanese patients.
Prosaposin, tumor‐secreted protein, promotes pancreatic cancer progression by decreasing tumor‐infiltrating lymphocytes
Authors: Miyahara Yoji , Takano Shigetsugu , Sogawa Kazuyuki , Tomizawa Satoshi , Furukawa Katsunori , Takayashiki Tsukasa , Kuboki Satoshi , Ohtsuka Masayuki
Published: May 2022

Glycoproteins produced by tumor cells are involved in cancer progression, metastasis, and the immune response, and serve as possible therapeutic targets. Considering the dismal outcomes of pancreatic ductal adenocarcinoma (PDAC) due to its unique tumor microenvironment, which is characterized by low antitumor T‐cell infiltration, we hypothesized that tumor‐derived glycoproteins may serve as regulating the tumor microenvironment. We used glycoproteomics with tandem mass tag labeling to investigate the culture media of three human PDAC cell lines, and attempted to identify the key secreted proteins from PDAC cells. Among the identified glycoproteins, prosaposin (PSAP) was investigated for its functional contribution to PDAC progression. PSAP is highly expressed in various PDAC cell lines; however, knockdown of intrinsic PSAP expression did not affect the proliferation and migration capacities. Based on the immunohistochemistry of resected human PDAC tissues, high PSAP expression was associated with poor prognosis in patients with PDAC. Notably, tumors with high PSAP expression showed significantly lower CD8+ T‐cell infiltration than those with low PSAP expression. Furthermore, PSAP stimulation decreased the proportion of CD8+ T cells in peripheral blood monocytes. Finally, in an orthotopic transplantation model, the number of CD8+ T cells in the PSAP shRNA groups was significantly increased, resulting in a decreased tumor volume compared with that in the control shRNA group. PSAP suppresses CD8+ T‐cell infiltration, leading to the promotion of PDAC progression. However, further studies are warranted to determine whether this study contributes to the development of a novel immunomodulating therapy for PDAC.
Bitten by the travelling bug: a review of toponymous contributions in dermatology
Authors: Sil Abheek , Gandhi Suneil , Das Anupam
Published: May 2022

The diverse world of dermatology has a wealth of protracted and at times tenuous names encompassing disease conditions, characteristic clinical descriptions and signs, among others. Many dermatological entities are identified by toponyms or place names. Although some sound irrelevant and archaic (with only historical importance reminding us of the lively history of the subject), other terminologies aid in easy recollection. In this review, we have succinctly summarized various toponymous description in dermatology covering diseases, signs, scales, criteria and treatments.
Eruptive naevi associated with encorafenib for metastatic colorectal cancer: two cases
Authors: Alfallouji Yasmin , Spencer Ashley , Calonje Eduardo , Perrett Conal M. , Watchorn Richard , Borysiewicz Catherine , Hodgkinson Tara , Wasan Harpreet , Bunker Christopher B. , Sidwell Rachel U.
Published: May 2022

Encorafenib is a BRAF inhibitor increasingly used as a second-line treatment for metastatic melanoma and colorectal cancer. BRAF inhibitors have been reported to be associated with new and changing melanocytic lesions, including eruptive naevi. We describe two cases of eruptive naevi secondary to encorafenib used for the treatment of BRAF-mutant metastatic colorectal cancer.
Local anaesthetics in dermatological surgery: a review of adjuncts and pain reduction techniques
Authors: Charalambides Maria , Yannoulias Basil , Gnanappiragasam Dushyanth , Veitch David , Wernham Aaron
Published: May 2022

A variety of adjuncts for local anaesthesia (LA) exists for dermatological surgery, along with many options to reduce the pain of LA. This review aims to summarize the evidence relating to such adjuncts and methods to reduce the pain of LA. Adjuncts to LA can be an important consideration to optimize anaesthetic effect. Current evidence suggests that buffering and warming of LA fluid, along with cooling, pinching and administering vibrations to the skin are effective at reducing pain during administration. In this review, no significant difference in pain reduction was found between cooling and administering vibrations to the skin. Studies demonstrate that, overall, LA injection into distal sites is safe. However, the evidence specific to dermatological surgery is limited with regard to ways to reduce pain during LA injection and in determining the safety of LA for distal sites with confidence. Further high-quality research in the form of multicentre randomized controlled trials is required.
On the definition of dermatological disease. Part 1: conceptual frameworks
Authors: Williams Hywel C.
Published: May 2022

Little attention is paid to disease definition in dermatology and how such definitions come about, yet defining a disease is a fundamental step upon which all subsequent clinical management and prognostic judgements depend. Developing diagnostic criteria is also a critically important step for research purposes so that studies referring to groups of people can be compared in a meaningful way. This short review introduces the concepts of regressive and progressive nosology, and how definitions of a dermatological disease can evolve in a useful way as knowledge about that disease increases. It also highlights the dangers of panchrestons – names that try to explain all yet end up explaining very little. It also considers approaches to disease definition, such as whether a binary yes/no or continuous approach is more appropriate. Conceptual frameworks including essentialistic vs. nominalistic approaches using the biomedical or biopsychosocial perspectives are articulated. The review then illustrates hazards of underdiagnosis and overdiagnosis, and introduces the notion of ‘disease mongering’ – the selling of disease in order to promote the use of medicines. The review concludes with a reaffirmation of the importance of defining dermatological disease, and why any new diagnostic criteria must be shown to increase predictive ability before they are assimilated into clinical practice and research.
A 5‐year randomized controlled trial comparing zirconia‐based versus metal‐based implant‐supported single‐tooth restorations in the premolar region
Authors: Hosseini Mandana , Worsaae Nils , Gotfredsen Klaus
Published: May 2022

Objective

To compare 5‐year biological, technical, aesthetic, and patient‐reported outcomes of single‐tooth implant‐supported all‐ceramic versus metal‐ceramic restorations.

Materials and methods

Thirty patients with 63 premolar agenesis participated in the 5‐year follow‐up. The prosthetic treatment on single‐tooth implants was randomly assigned to all‐ceramic crowns on zirconia abutments (AC = 31) or metal‐ceramic crowns on metal abutments (MC = 32). All patients were recalled to clinical examinations at baseline, 1, 3, and 5 years after prosthetic treatments. Biological, technical, and aesthetic outcomes including complications were clinically and radiographically registered. The patient‐reported outcomes were recorded using OHIP‐49 questionnaire before treatment and at each follow‐up examination.

Results

At the 5‐year examination, the survival rate was 100% for implants and 100% for AC and 97% for MC crowns and abutments. The marginal bone loss after 5 years was minor and not significantly different (p = .056) between AC (mean: 0.3,SD: 1.1) and MC (mean: −0.1,SD: 0.4) restorations. The success rate of the implants based on marginal bone loss was 77.4% for AC‐ and 93.7% for MC restorations. The marginal adaptation was significantly better for MC than for AC restorations (p = .025). The aesthetic outcomes and patient‐reported outcomes between AC and MC restorations were not significantly different.

Conclusions

The biological, aesthetic and patient‐reported outcomes for implant‐supported AC and MC restorations were successful and with no significant difference after 5‐years. The marginal adaptation of the MC crowns cemented on titanium abutments showed a significantly better fit than restorations based on zirconia crowns cemented on zirconia abutments.
SUMOylation of Kir7.1 participates in neuropathic pain through regulating its membrane expression in spinal cord neurons
Authors: Lv You‐You , Wang Han , Fan Hai‐Ting , Xu Ting , Xin Wen‐Jun , Guo Rui‐Xian
Published: May 2022

Aims

Potassium (K+) channels have been demonstrated to play a prominent involvement in nociceptive processing. Kir7.1, the newest members of the Kir channel family, has not been extensively studied in the CNS, and its function remains largely unknown. The present study investigated the role of spinal Kir7.1 in the development of pathological pain.

Methods and Results

Neuropathic pain was induced by spared nerve injury (SNI). The mechanical sensitivity was assessed by von Frey test. Immunofluorescence staining assay revealed that Kir7.1 was predominantly expressed in spinal neurons but not astrocytes or microglia in normal rats. Western blot results showed that SNI markedly decreased the total and membrane expression of Kir7.1 in the spinal dorsal horn accompanied by mechanical hypersensitivity. Blocking Kir7.1 with the specific antagonist ML418 or knockdown kir7.1 by siRNA led to mechanical allodynia. Co‐IP results showed that the spinal kir7.1 channels were decorated by SUMO‐1 but not SUMO‐2/3, and Kir7.1 SUMOylation was upregulated following SNI. Moreover, inhibited SUMOylation by GA (E1 inhibitor) or 2‐D08 (UBC9 inhibitor) can increase the spinal surface Kir7.1 expression.

Conclusion

SUMOylation of the Kir7.1 in the spinal cord might contribute to the development of SNI‐induced mechanical allodynia by decreasing the Kir7.1 surface expression in rats.
Somatostatin signalling promotes the differentiation of rod photoreceptors in human pluripotent stem cell‐derived retinal organoid
Authors: Chen Mingkang , Mao Xiying , Huang Darui , Jing Jiaona , Zou Wenjun , Mao Peiyao , Xue Mengting , Yin Wenjie , Cheng Ruiwen , Gao Yan , Hu Youjin , Yuan Songtao , Liu Qinghuai
Published: May 2022

Objectives

Stem cell‐derived photoreceptor replacement therapy is a promising strategy for the treatment of retinal degenerative disease. The development of 3D retinal organoids has permitted the production of photoreceptors. However, there is no strategy to enrich a specific photoreceptor subtype due to inadequate knowledge of the molecular mechanism underlying the photoreceptor fate determination. Hence, our aim is to explore the uncharacterized function of somatostatin signalling in human pluripotent stem cell‐derived photoreceptor differentiation.

Materials and Methods

3D retinal organoids were achieved from human embryonic stem cell. The published single‐cell RNA‐sequencing datasets of human retinal development were utilized to further investigate the transcriptional regulation of photoreceptor differentiation. The assays of immunofluorescence staining, lentivirus transfection, real‐time quantitative polymerase chain reaction and western blotting were performed.

Results

We identified that the somatostatin receptor 2 (SSTR2)‐mediated signalling was essential for rod photoreceptor differentiation at the precursor stage. The addition of the cognate ligand somatostatin in human 3D retinal organoids promoted rod photoreceptor differentiation and inhibited cone photoreceptor production. Furthermore, we found that the genesis of rod photoreceptors was modulated by endogenous somatostatin specifically secreted by developing retinal ganglion cells.

Conclusions

Our study identified SSTR2 signalling as a novel extrinsic regulator for rod photoreceptor fate determination in photoreceptor precursors, which expands the repertoire of functional signalling pathways in photoreceptor development and sheds light on the optimization of the photoreceptor enrichment strategy.
Outcomes of dual kidney transplants from high KDPI kidneys are superior compared to single kidney high KDPI transplants at 1 year
Authors: Das Devika , Wagler Josiah , Ohara Stephanie , Nguyen Michelle , Frasco Peter E. , Smith Maxwell , Khamash Hasan , Mathur Amit K. , Budhiraja Pooja , Reddy Kunam , Heilman Raymond , Jadlowiec Caroline
Published: May 2022

Dual kidney transplantation (DKT), utilizing two adult kidneys from the same donor for one recipient, has been used as a way to expand the available donor pool. These kidneys often come from high Kidney Donor Profile Index donors (KDPI > 85%). Data comparing outcomes between high KDPI DKT and single kidney transplants (SKT) remain limited. We assessed outcomes of 336 high KDPI kidney transplants performed at our center; 11.0% (n = 37) were DKT. Recipients of DKT were older (P = .02) and donors had a higher KDPI score (median 96% vs. 91%, P < .0001). DKT operative time was higher compared to SKT (+1.4 hours, P < .0001). There were no differences in delayed graft function (54.1% vs. 51.5%, P = .77) and hospital length of stay (median 4.0 vs. 3.0 days, P = .21) between DKT and SKT. Grade I Clavien‐Dindo complications occurred in 8.1% of DKT and 13.7% of SKT (P = .008). There were no grade IVa, IVb, or V complications in either group. DKT had more glomerulosclerosis (P = .04), interstitial fibrosis (P = .02), tubular atrophy (P = .01), and arterial thickening (P = .03) on 1‐year protocol biopsies. Estimated glomerular filtration was higher for DKT at 1‐ (P = .004) and 2‐years post‐transplant (P = .01). There were no differences in patient (HR 1.3, 95% CI .5‐3.3, P = .58) or graft (HR 1.1, 95% CI .5‐2.3, P = .83) survival. Good outcomes can be achieved with DKT using high KDPI kidneys with moderate chronic changes. DKT is a good option to help further utilize high KDPI kidneys and minimize discard.