bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute generalised exanthematous pustulosis: an unusual cause of carpal tunnel syndrome
Authors: Lim Xuxin , Wong Kai Yuen
Published: January 2021

A 65-year-old man presented with generalised erythematous pustular rash following an insect bite. He was initially treated with antibiotics for presumed cellulitis. He subsequently developed bilateral carpal tunnel syndrome. Skin biopsy confirmed a diagnosis of acute generalised exanthematous pustulosis, which resolved with oral prednisolone. He also had steroid injections for his bilateral carpal tunnel syndrome and this recovered uneventfully. Clinical presentation, histological assessment and EuroSCAR criteria were key to the diagnosis and management of this case.
Solitary neurofibroma of the larynx: a diagnostic challenge
Authors: Cunha Bruno , Pacheco Ricardo , Fonseca Isabel , Borges Alexandra
Published: January 2021

Solitary neurofibromas of the larynx are extremely rare, with a total of 15 cases described in the literature. Nonetheless, acquaintance with this diagnosis is important, as misdiagnoses can have negative consequences. Presenting symptoms are non-specific and depend on tumour size and location. As well-defined submucosal masses with a broad differential diagnosis, they remain a clinical and radiological challenge. While some characteristics might favour a benign nature and subtle signs might help narrow the differential diagnosis, imaging alone is not sufficient for differentiation and definitive diagnosis requires a biopsy. Complete surgical resection and long-term follow-up is indicated. We share our experience on a case of a solitary laryngeal neurofibroma in a middle-aged woman, presenting with a large well-defined paraglottic lesion.
Profound diarrhoea and weight loss in an immunocompromised patient
Authors: Ashton George , Shand Alan , Arnott Ian , Din Shahida
Published: January 2021

A 75-year-old man was admitted with a 3-month history of worsening diarrhoea and weight loss. He was on long-term immunosuppression following cardiac transplantation. Investigations revealed herpes simplex oesophagitis and stool samples were positive for norovirus. Treatment with acyclovir and nitazoxanide resulted in a complete resolution of symptoms. Norovirus is a common cause of infectious gastroenteritis, but immunosuppressed patients may present with chronic diarrhoea rather than an acute illness. This case highlights the importance of a low clinical threshold for testing for norovirus infection in immunocompromised patients.
Systemic generalised lymphangiomatosis: unknown aetiology and a challenge to treat
Authors: Van Meerhaeghe Tess , Vandenbroucke Frederik , Velkeniers Brigitte
Published: January 2021

We describe a case of a woman diagnosed at the age of 35 years with a generalised mediastinal and abdominal lymphangiomatosis associated with a protein losing enteropathy, who successfully improved when treatment with sirolimus was initiated.
Dual mutation (MTHFR A1298C with PAI (4G) mutation) manifesting with bilateral lower limb gangrene in a neonate
Authors: Kumar Ashutosh , Ramachandran Sateesh , Swain Pranati , Negi Vandana
Published: January 2021

Neonates are at highest risk of thrombosis among paediatric patients. The relative prothrombotic state in a well neonate is compensated by other factors preventing spontaneous thrombosis; however, in a neonate with genetic predisposition, the balance is tilted predisposing them to a life-threatening thrombotic episode. We describe a rare case of methylenetetrahydrofolate reductase A1298C (homozygous) mutation along with plasminogen activator inhibitor (4G) mutation in a neonate who developed bilateral lower limb gangrene following thrombosis of the iliac vessels without any triggering factor. The neonate underwent thrombectomy as debulking measure along with thrombolytic therapy followed by unfractionated heparin and low-molecular-weight heparin which is still being continued along with oral aspirin. The neonate had to undergo amputation of both the involved lower limbs in view of dry gangrene. This case highlights that the dual mutations causing the prothrombotic state predispose the individual to the spontaneous life-threatening thrombotic episode as compared with the single mutation.
New onset adrenal insufficiency in a patient with COVID-19
Authors: Hashim Maram , Athar Syed , Gaba Waqar Haider
Published: January 2021

SARS-CoV-2 is the cause of COVID-19. Since the outbreak and rapid spread of COVID-19, it has been apparent that the disease is having multi-organ system involvement. Still its effect in the endocrine system is not fully clear and data on cortisol dynamics in patients with COVID-19 are not yet available. SARS-CoV-2 can knock down the host’s cortisol stress response. Here we present a case of a 51-year-old man vomiting for 10 days after having confirmed COVID-19 infection. He had hypotension and significant hyponatraemia. Work-up was done including adrenocorticotropic hormone stimulation test. He was diagnosed as suffering from adrenal insufficiency and started on steroids with subsequent improvement in both blood pressure and sodium level. COVID-19 can cause adrenal insufficiency. Clinicians must be vigilant about the possibility of an underlying relative cortisol deficiency in patients with COVID-19.
Cerebral salt-wasting syndrome in a patient with status epilepticus: a rare association
Authors: Tale Sudheer , Kolli Mrudula , Masaipeta Kesari , Budumuri Gautam Vinay Kumar
Published: January 2021

Hyponatraemia is one of the most common and serious electrolyte abnormalities in patients with neurological diseases. Assessing the intravascular fluid status, urine sodium, urine and serum osmolality helps to narrow down the differential diagnosis. Differentiation between cerebral salt-wasting syndrome (CSWS), diabetes insipidus and syndrome of inappropriate antidiuretic hormone (SIADH) secretion is absolutely necessary for correct management of hyponatraemia in this group of patients. In this case report, we have presented a 46-year-old gentleman who was admitted to intensive care unit (ICU) with status epilepticus and developed hyponatraemia during course of his ICU stay, diagnosed as CSWS and managed with normal saline and fludrocortisone. His serum sodium gradually improved, consciousness was regained and later shifted to general ward on antiepileptic treatment.
Incidental finding of regressed solitary unilateral choroidal metastasis from lung adenocarcinoma with EGFR exon-19 deletion treated with erlotinib
Authors: Padhy Srikanta Kumar , Kaliki Swathi
Published: January 2021

A 49-year-old Asian Indian woman, with a previous history of biopsy proven stage IV primary lung adenocarcinoma with metastasis to liver, bones and central nervous system, presented with 1-month history of photopsia in right eye. She was on oral erlotinib since 6 months. Dilated fundus examination of right eye revealed a solitary dome-shaped brownish elevated lesion of approximately 1-disc diameter along the inferotemporal midperiphery with surrounding areas of hypopigmentation. Based on multimodal imaging, a diagnosis of resolved solitary unilateral choroidal metastasis from lung carcinoma in the right eye was made. In view of inactive and regressed choroidal metastasis, no intervention was mandated.
Leiomyosarcoma of the inferior vena cava posing as an adrenal incidentaloma
Authors: Ramanan Sinduja , Munuswamy Hemachandren , Nelamangala Ramakrishnaiah Vishnu Prasad , Toi Pampa Ch
Published: January 2021

Adrenal incidentalomas are incidentally detected adrenal lesions on imaging, which have a variety of differential diagnoses, the most common being a non-functioning adenoma. Surgical intervention for these lesions is needed when there is hypersecretion, for lesions larger than 4 cm and smaller lesions with suspicious characteristics. Here we present a young woman who was incidentally found to have a right suprarenal mass with loss of fat planes with the inferior vena cava (IVC). She underwent resection of the tumour along with the posterior wall of IVC, which was primarily repaired. Her postoperative biopsy was suggestive of leiomyosarcoma arising from the IVC. In the absence of distant metastasis, the sole prognostic factor for this tumour is achieving negative margins through radical resection of the tumour with IVC resection. Retroperitoneal leiomyosarcomas should be considered as a differential diagnosis for larger lesions, especially those more than 10 cm.
Unusual presentation of superior mesenteric artery syndrome after trauma
Authors: Byreddi Laxman Yashwant , Dutta Arunima , Kesari Kavitha
Published: January 2021

Superior mesenteric artery (SMA) syndrome is a rare but severe condition. SMA syndrome’s association with trauma has been reported to present weeks to months after significant weight loss due to head or spinal cord injury. We present an unusual case of SMA syndrome presenting with obstructive symptoms, which developed immediately after clavicle fracture and was not associated with weight loss. CT of the abdomen showed small bowel obstruction in the third part of the duodenum. CT angiogram of the abdomen confirmed SMA syndrome. The patient was managed conservatively with enteral nutrition via jejunostomy tube. He was discharged after symptoms resolved, and repeat imaging revealed resolution of obstruction. This case emphasises the importance of having SMA syndrome as one of the differential diagnoses for patients presenting with obstructive symptoms after trauma because early diagnosis can be managed with conservative treatment.
Choroidal neovascularisation following inverted internal limiting membrane flap technique for idiopathic macular hole: a case for modified flaps
Authors: Gupta Nikita , Mehta Aditi , Dogra Mohit , Singh Simar Rajan
Published: January 2021

A 70-year-old woman presented with sudden decrease of vision 2 months following a successful vitrectomy with inverted internal limiting membrane flap for a full thickness macular hole. Serial review of fundus pictures and optical coherence tomography scans revealed a focal retinal pigment epithelial disruption at the site of the macular hole after surgery and a choroidal neovascular membrane arising from the same. This report describes the possible role of the surgical technique in causation of the membrane and discusses modifications to avoid the same.
FulminantBacillus cereusfood poisoning with fatal multi-organ failure
Authors: Colaco Clinton M G , Basile Kerri , Draper Jenny , Ferguson Patricia E
Published: January 2021

This case represents a rare fulminant course of fried-rice associated food poisoning in an immunocompetent person due to pre-formed exotoxin produced byBacillus cereus, with severe manifestations of sepsis, including multi-organ (hepatic, renal, cardiac, respiratory and neurological) failure, shock, metabolic acidosis, rhabdomyolysis and coagulopathy. Despite maximal supportive measures (continuous renal replacement therapy, plasmapheresis, N-acetylcysteine infusion and blood products, and broad-spectrum antimicrobials) and input from a multidisciplinary team (consisting of infectious diseases, intensive care, gastroenterology, surgery, toxicology, immunology and haematology), mortality resulted. This case is the first to use whole genome sequencing techniques to confirm the toxigenic potential ofB. cereus. It has important implications for food preparation and storage, particularly given its occurrence in home isolation during the COVID-19 pandemic.
Cystic biliary atresia with congenital absence of portal vein
Authors: Nandan Ruchira , Jana Manisha , Yadav Devendra Kumar , Goel Prabudh
Published: January 2021

A 126-day female child presented with jaundice since day 7 of life. She was icteric and had hepatosplenomegaly. Radiological investigations revealed three extrahepatic and multiple intrahepatic biliary cysts, absent gall bladder and portal vein. These findings were confirmed on laparotomy. To the best of our knowledge, this is the first report of cystic biliary atresia associated with congenital absence of portal vein.
Atrial fibrillation following low voltage electrical injury
Authors: Ghosh Shrestha , Chandra Atanu , Sen Sourav , Dutta Sukanta
Published: January 2021

Electrical injuries can have myriad presentations, including significant cardiac involvement. Arrhythmias are the most frequently experienced cardiac affliction, of which sinus tachycardia or bradycardia, ventricular fibrillation, atrial or ventricular premature beats and bundle branch block are most commonly reported. A 50-year-old man, with no prior history of cardiac disease, presented with palpitations following low voltage electrical injury. On examination, he was tachycardic with an irregularly irregular pulse. An ECG confirmed atrial fibrillation with rapid ventricular rate. Chemical cardioversion was attempted successfully, following which the patient reverted to sinus rhythm. Atrial fibrillation following electrical injury has been rarely described in the literature, and is rarer so without associated high voltage electrical exposure or pre-existing cardiac ailment.
Post-traumatic bilateral posterior hip dislocations with femoral head fracture on one side and acetabular fracture on the other side: a very rare presentation
Authors: Hegde Atmananda , Mane Prajwal Prabhudev , Khanna Vikrant , Rao Seetharama
Published: January 2021

Hip dislocations are common orthopaedic emergencies which need early intervention to have a better outcome. They usually occur as a result of high energy trauma with motor vehicle accidents being the most common cause followed by fall from height. Posterior hip dislocation is more common than anterior. However, bilateral hip dislocations are rare compared with unilateral. Here we report our case with bilateral posterior hip dislocation with one side having head of femur fracture and contralateral side acetabulum fracture. Both hips were reduced under general anaesthesia on the same day of the trauma. Staged definitive treatment was carried out. The patient had an early recovery with no complications. This case represents an unusual, type of injury resulting from a high speed motor vehicle accident. Early diagnosis, immediate resuscitation and reduction of the hip joints followed by a careful and planned definitive treatment is necessary to have a better outcome.
Late onset of Guillain-Barré syndrome following SARS-CoV-2 infection: part of ‘long COVID-19 syndrome’?
Authors: Raahimi Mina M , Kane Alice , Moore Christopher EG , Alareed Ahmad W
Published: January 2021

We describe a case of delayed onset, acute demyelinating neuropathy secondary to novel SARS-CoV-2 infection. A previously healthy 46-year-old man presented with bilateral leg pain and loss of sensation in his feet 53 days after having COVID-19 pneumonitis. He developed painful sensory symptoms followed by a rapidly progressive lower motor neuron weakness involving all limbs, face and respiratory muscles, needing ventilatory support. In keeping with a diagnosis of Guillain-Barré syndrome, cerebrospinal fluid examination showed albuminocytologic dissociation and nerve conduction studies supported the diagnosis of an acute inflammatory demyelinating polyradiculoneuropathy. The delayed neurological dysfunction seen in our patient following SARS-CoV-2 infection may indicate a novel mechanism of disease that is part of the emerging ‘long COVID-19 syndrome’.
Bleeding complications of thromboprophylaxis with dabigatran, nadroparin or rivaroxaban for 6 weeks after total knee arthroplasty surgery: a randomised pilot study
Authors: van der Veen Lucia , Segers Marijn , van Raay Jos JAM , Gerritsma-Bleeker Carina LE , Brouwer Reinoud W , Veeger Nic JGM , van Hulst Marinus
Published: January 2021

Objectives

For the non-vitamin-K oral anticoagulants, data on bleeding when used for 42 days as thromboprophylaxis after total knee arthroplasty (TKA) are scarce. This pilot study assessed feasibility of a multicentre randomised clinical trial to evaluate major and clinically relevant non-major bleeding during 42-day use of dabigatran, nadroparin and rivaroxaban after TKA.

Patients and methods

In 70 weeks, between July 2012 and November 2013, 198 TKA patients were screened for eligibility in the Martini Hospital (Groningen, the Netherlands). Patients were randomly assigned to dabigatran (n=45), nadroparin (n=45) or rivaroxaban (n=48). The primary outcome was the combined endpoint of major bleeding and clinically relevant non-major bleeding. Secondary endpoints of this study were the occurrence of clinical venous thromboembolism (VTE) (pulmonary embolism or deep venous thrombosis), compliance, duration of hospital stay, rehospitalisation, adverse events and Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

The primary outcome was observed in 33.3% (95% CI 20.0% to 49.0%), 24.4% (95% CI 12.9% to 39.5%) and 27.1% (95% CI 15.3% to 41.8%) of patients who received dabigatran, nadroparin or rivaroxaban, respectively (p=0.67). Major bleeding was found in two patients who received nadroparin (p=0.21). Clinically relevant non-major bleeding was observed in 33.3% (95% CI 20.0% to 49.0%), 22.2% (95% CI 11.2% to 37.1%) and 27.1% (95% CI 15.3% to 41.8%) for dabigatran, nadroparin and rivaroxaban, respectively (p=0.51). Wound haematoma was the most observed bleeding event. VTE was found in one patient who received dabigatran (p=0.65). The presurgery and postsurgery KOOS qQuestionnaires were available for 32 (71%), 35 (77%) and 35 (73%) patients for dabigatran, nadroparin and rivaroxaban, respectively. KOOS was highly variable, and no significant difference between treatment groups in mean improvement was observed.

Conclusions

A multicentre clinical trial may be feasible. However, investments will be substantial. No differences in major and clinically relevant non-major bleeding events were found between dabigatran, nadroparin and rivaroxaban during 42 days after TKA. KOOS may not be suitable to detect functional loss due to bleeding.

Trial registration number

NCT01431456.
Internal consistency and factor structure of Jenkins Sleep Scale: cross-sectional cohort study among 80 000 adults
Authors: Juhola Juhani , Arokoski J P A , Ervasti Jenni , Kivimäki Mika , Vahtera Jussi , Myllyntausta Saana , Saltychev M
Published: January 2021

Objectives

To assess the internal consistency and construct validity of the Finnish translation of the Jenkins Sleep Scale (JSS) in a large healthy working-age population with diverse work characteristics.

Design

Survey-based cross-sectional cohort study.

Setting

Survey conducted by an institute of occupational health.

Participants

Employees of 10 towns and 6 hospital districts.

Primary and secondary outcome measures

The internal consistency defined by a Cronbach’s alpha. Exploratory and confirmatory factor analyses to evaluate the construct structure of the JSS.

Results

Of 81 136 respondents, 14 890 (18%) were men and 66 246 (82%) were women. Their average age was 52.1 (13.2) years. Of the respondents, 41 823 (52%) were sleeping 7 or less hours per night. The mean JSS total score was 6.4 (4.8) points. The JSS demonstrated high internal consistency with an alpha of 0.80 (lower 95% confidence limit 0.80). Exploratory factor analysis supported a one-factor solution with eigenvalue of 1.94. Confirmatory factor analysis showed that all four items were positively correlated with a single common factor explaining 44%–61% of common factor’s variance.

Conclusions

The Finnish translation of JSS was found to be a unidimensional scale with good internal consistency. As such, the scale may be recommended as a practicable questionnaire when studying sleep difficulties in a healthy working-age population.
Factors associated with adherence to COVID-19 prevention measures in the Democratic Republic of the Congo (DRC): results of an online survey
Authors: Ditekemena John Dinanga , Nkamba Dalau Mukadi , Muhindo Hypolite Mavoko , Siewe Joseph Nelson Fodjo , Luhata Christophe , Van den Bergh Rafael , Tshefu Kitoto Antoinette , Van Damme Wim , Muyembe Jean Jacques , Colebunders Robert
Published: January 2021

Objectives

We aimed to assess the level of adherence to COVID-19 preventive measures in the Democratic Republic of the Congo (DRC) and to identify factors associated with non-adherence.

Design

A cross-sectional population-based online survey.

Settings

The study was conducted in 22 provinces of the DRC. Five provinces with a satisfactory number of respondents were included in the analysis: Haut Katanga, Kasaï-Central, Kasaï-Oriental, Kinshasa and North Kivu.

Participants

The participants were people aged ≥18 years, living in the DRC. A total of 3268 participants were included in the study analysis.

Interventions

Both convenience sampling (surveyors themselves contacted potential participants in different districts) and snowball sampling (the participants were requested to share the link of the questionnaire with their contacts) methods were used.

Primary and secondary outcome measures

We computed adherence scores using responses to 10 questions concerning COVID-19 preventive measures recommended by the WHO and the DRC Ministry of Health. We used logistic regression analysis with generalised estimating equations to identify factors of poor adherence. We also asked about the presence or absence of flu-like symptoms during the preceding 14 days, whether a COVID-19 test was done and the test result.

Results

Data from 3268 participants were analysed. Face masks were not used by 1789 (54.7%) participants. Non-adherence to physical distancing was reported by 1364 (41.7%) participants. 501 (15.3%) participants did not observe regular handwashing. Five variables were associated with poor adherence: lower education level, living with other people at home, being jobless/students, living with a partner and not being a healthcare worker.

Conclusion

Despite compulsory restrictions imposed by the government, only about half of the respondents adhered to COVID-19 preventive measures in the DRC. Disparities across the provinces are remarkable. There is an urgent need to further explore the reasons for these disparities and factors associated with non-adherence.
Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial
Authors: Yaskolka Meir Anat , Rinott Ehud , Tsaban Gal , Zelicha Hila , Kaplan Alon , Rosen Philip , Shelef Ilan , Youngster Ilan , Shalev Aryeh , Blüher Matthias , Ceglarek Uta , Stumvoll Michael , Tuohy Kieran , Diotallevi Camilla , Vrhovsek Urska , Hu Frank , Stampfer Meir , Shai Iris
Published: January 2021

Objective

To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss.

Design

For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3–4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS).

Results

Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18-month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups. Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (−38.9% proportionally), as compared with MED (−19.6% proportionally; p=0.035 weight loss adjusted) and HDG (−12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic-acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all).

Conclusion

The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half.

Trial registration number

NCT03020186.
Blocking IL-17A enhances tumor response to anti-PD-1 immunotherapy in microsatellite stable colorectal cancer
Authors: Liu Chao , Liu Ruiqi , Wang Bojun , Lian Jie , Yao Yang , Sun Haoxiu , Zhang Chunhui , Fang Lin , Guan Xin , Shi Jiaqi , Han Shuling , Zhan Fei , Luo Shengnan , Yao Yuanfei , Zheng Tongsen , Zhang Yanqiao
Published: January 2021

Background

Immune checkpoint inhibitors (ICIs), including anti-PD-1 therapy, have limited efficacy in patients with microsatellite stable (MSS) colorectal cancer (CRC). Interleukin 17A (IL-17A) activity leads to a protumor microenvironment, dependent on its ability to induce the production of inflammatory mediators, mobilize myeloid cells and reshape the tumor environment. In the present study, we aimed to investigate the role of IL-17A in resistance to antitumor immunity and to explore the feasibility of anti-IL-17A combined with anti-PD-1 therapy in MSS CRC murine models.

Methods

The expression of programmed cell death-ligand 1 (PD-L1) and its regulation by miR-15b-5p were investigated in MSS CRC cell lines and tissues. The effects of miR-15b-5p on tumorigenesis and anti-PD-1 treatment sensitivity were verified both in vitro and in colitis-associated cancer (CAC) and APCmin/+murine models. In vivo efficacy and mechanistic studies were conducted using antibodies targeting IL-17A and PD-1 in mice bearing subcutaneous CT26 and MC38 tumors.

Results

Evaluation of clinical pathological specimens confirmed thatPD-L1mRNA levels are associated with CD8+ T cell infiltration and better prognosis. miR-15b-5p was found to downregulate the expression of PD-L1 at the protein level, inhibit tumorigenesis and enhance anti-PD-1 sensitivity in CAC and APCmin/+CRC models. IL-17A led to high PD-L1 expression in CRC cells through regulating the P65/NRF1/miR-15b-5p axis. Combined IL-17A and PD-1 blockade had efficacy in CT26 and MC38 tumors, with more cytotoxic T lymphocytes cells and fewer myeloid-derived suppressor cells in tumors.

Conclusions

IL-17A increases PD-L1 expression through the p65/NRF1/miR-15b-5p axis and promotes resistance to anti-PD-1 therapy. Blocking IL-17A improved the efficacy of anti-PD-1 therapy in MSS CRC murine models. IL-17A might serve as a therapeutic target to sensitize patients with MSS CRC to ICI therapy.
Estrogen receptor beta signaling in CD8+ T cells boosts T cell receptor activation and antitumor immunity through a phosphotyrosine switch
Authors: Yuan Bin , Clark Curtis A , Wu Bogang , Yang Jing , Drerup Justin M , Li Tianbao , Jin Victor X , Hu Yanfen , Curiel Tyler J , Li Rong
Published: January 2021

Background

The non-overlapping functions of the two estrogen receptor subtypes, ERα (Estrogen Receptor α)and ERβ (Estrogen Receptor β), in tumor cells have been studied extensively. However, their counterparts in host cells is vastly underinterrogated. Even less is known about how ERα and ERβ activities are regulated in a subtype-specific manner. We previously identified a phosphotyrosine residue (pY36) of human ERβ that is important for tumor ERβ to inhibit growth of breast cancer cells in vitro and in vivo. A role of this ERβ phosphotyrosine switch in regulating host ERβ remains unclear.Conventional gene editing was used to mutate the corresponding tyrosine residue of endogenous mouse ERβ (Y55F) in mouse embryonic stem cells. The derived homozygous mutant Esr2Y55F/Y55F mouse strain and its wild-type (WT) counterpart were compared in various transplant tumor models for their ability to support tumor growth. In addition, flow cytometry-based immunophenotyping was carried out to assess antitumor immunity of WT and mutant hosts. Adoptive transfer of bone marrow and purified CD8+ T cells were performed to identify the host cell type that harbors ERβ-dependent antitumor function. Furthermore, cell signaling assays were conducted to compare T cell receptor (TCR)-initiated signaling cascade in CD8+ T cells of WT and mutant mice. Lastly, the ERβ-selective agonist S-equol was evaluated for its efficacy to boost immune checkpoint blockade (ICB)-based anticancer immunotherapy.Disabling the ERβ-specific phosphotyrosine switch in tumor-bearing hosts exacerbates tumor growth. Further, a cell-autonomous ERβ function was defined in CD8+ effector T cells. Mechanistically, TCR activation triggers ERβ phosphorylation, which in turn augments the downstream TCR signaling cascade via a non-genomic action of ERβ. S-equol facilitates TCR activation that stimulates the ERβ phosphotyrosine switch and boosts anti-PD-1 (Programmed cell death protein 1) ICB immunotherapy.

Our mouse genetic study clearly demonstrates a role of the ERβ phosphotyrosine switch in regulating ERβ-dependent antitumor immunity in CD8+ T cells. Our findings support the development of ERβ agonists including S-equol in combination with ICB immunotherapy for cancer treatment.
Clinical exome sequencing data reveal high diagnostic yields for congenital diaphragmatic hernia plus (CDH+) and new phenotypic expansions involving CDH
Authors: Scott Tiana M , Campbell Ian M , Hernandez-Garcia Andres , Lalani Seema R , Liu Pengfei , Shaw Chad A , Rosenfeld Jill A , Scott Daryl A
Published: January 2021

Background

Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect that often co-occurs with non-hernia-related anomalies (CDH+). While copy number variant (CNV) analysis is often employed as a diagnostic test for CDH+, clinical exome sequencing (ES) has not been universally adopted.

Methods

We analysed a clinical database of ~12 000 test results to determine the diagnostic yields of ES in CDH+ and to identify new phenotypic expansions.

Results

Among the 76 cases with an indication of CDH+, a molecular diagnosis was made in 28 cases for a diagnostic yield of 37% (28/76). A provisional diagnosis was made in seven other cases (9%; 7/76). Four individuals had a diagnosis of Kabuki syndrome caused by frameshift variants inKMT2D. Putatively deleterious variants inALG12andEP300were each found in two individuals, supporting their role in CDH development. We also identified individuals with de novo pathogenic variants inFOXP1andSMARCA4, and compound heterozygous pathogenic variants inBRCA2. The role of these genes in CDH development is supported by the expression of their mouse homologs in the developing diaphragm, their high CDH-specific pathogenicity scores generated using a previously validated algorithm for genome-scale knowledge synthesis and previously published case reports.

Conclusion

We conclude that ES should be ordered in cases of CDH+ when a specific diagnosis is not suspected and CNV analyses are negative. Our results also provide evidence in favour of phenotypic expansions involving CDH for genes associated withALG12-congenital disorder of glycosylation, Rubinstein-Taybi syndrome, Fanconi anaemia, Coffin-Siris syndrome andFOXP1-related disorders.
CHARGE-AF in a national routine primary care electronic health records database in the Netherlands: validation for 5-year risk of atrial fibrillation and implications for patient selection in atrial fibrillation screening
Authors: Himmelreich Jelle C L , Lucassen Wim A M , Harskamp Ralf E , Aussems Claire , van Weert Henk C P M , Nielen Mark M J
Published: January 2021

Aims

To validate a multivariable risk prediction model (Cohorts for Heart and Aging Research in Genomic Epidemiology model for atrial fibrillation (CHARGE-AF)) for 5-year risk of atrial fibrillation (AF) in routinely collected primary care data and to assess CHARGE-AF’s potential for automated, low-cost selection of patients at high risk for AF based on routine primary care data.

Methods

We included patients aged ≥40 years, free of AF and with complete CHARGE-AF variables at baseline, 1 January 2014, in a representative, nationwide routine primary care database in the Netherlands (Nivel-PCD). We validated CHARGE-AF for 5-year observed AF incidence using the C-statistic for discrimination, and calibration plot and stratified Kaplan-Meier plot for calibration. We compared CHARGE-AF with other predictors and assessed implications of using different CHARGE-AF cut-offs to select high-risk patients.

Results

Among 111 475 patients free of AF and with complete CHARGE-AF variables at baseline (17.2% of all patients aged ≥40 years and free of AF), mean age was 65.5 years, and 53% were female. Complete CHARGE-AF cases were older and had higher AF incidence and cardiovascular comorbidity rate than incomplete cases. There were 5264 (4.7%) new AF cases during 5-year follow-up among complete cases. CHARGE-AF’s C-statistic for new AF was 0.74 (95% CI 0.73 to 0.74). The calibration plot showed slight risk underestimation in low-risk deciles and overestimation of absolute AF risk in those with highest predicted risk. The Kaplan-Meier plot with categories <2.5%, 2.5%–5% and >5% predicted 5-year risk was highly accurate. CHARGE-AF outperformed CHA2DS2-VASc (Cardiac failure or dysfunction, Hypertension, Age >=75 [Doubled], Diabetes, Stroke [Doubled]-Vascular disease, Age 65-74, and Sex category [Female]) and age alone as predictors for AF. Dichotomisation at cut-offs of 2.5%, 5% and 10% baseline CHARGE-AF risk all showed merits for patient selection in AF screening efforts.

Conclusion

In patients with complete baseline CHARGE-AF data through routine Dutch primary care, CHARGE-AF accurately assessed AF risk among older primary care patients, outperformed both CHA2DS2-VASc and age alone as predictors for AF and showed potential for automated, low-cost patient selection in AF screening.
Impaired coronary flow velocity reserve is associated with cardiovascular risk factors but not with angina symptoms
Authors: Bove Kira Bang , Michelsen Marie M , Schroder Jakob , Suhrs Hannah Elena , Bechsgaard Daria F , Mygind Naja Dam , Aziz Ahmed , Kastrup Jens , Gustafsson Ida , Prescott Eva
Published: January 2021

Objectives

Coronary microvascular dysfunction (CMD) is considered to cause angina pectoris in a large proportion of women with no obstructive coronary artery disease (CAD). However, data supporting a relation between angina pectoris and CMD are limited. We compared CMD in women with angina with asymptomatic women and evaluated the relation between presence of CMD, angina characteristics, cardiovascular risk factors and results of stress testing.

Methods

In a cross-sectional study, we included 1684 women with angina and <50% coronary artery stenosis on invasive angiography. Asymptomatic women from the community-based Copenhagen City Heart Study served as reference group (n=102). Coronary microvascular function was determined by coronary flow velocity reserve (CFVR) assessed by transthoracic Doppler stress echocardiography. CFVR < 2 was defined as CMD. Symptoms were obtained from standardised angina questionnaires and results of stress testing from health records.

Results

Median CFVR was 2.33 (IQR 2.00–2.75) in symptomatic women versus 2.60 (2.19–2.95) in asymptomatic (p=0.007). CFVR <2 was found in 25% of symptomatic and in 19% of asymptomatic women. Symptomatic women had a greater risk factor burden. After adjusting for age, hypertension, diabetes, smoking and heart rate the difference in CFVR between groups disappeared (p=0.213). We found no associations between CFVR and angina characteristics, symptom burden or results from stress testing.

Conclusions

Impaired CFVR is more prevalent in symptomatic than in asymptomatic women and related to the cardiovascular risk factors hypertension, diabetes, smoking and increased heart rate. Neither a positive bicycle test, single photon emission CT stress test nor chest pain characteristics identify women with impaired CFVR among women with angina and no obstructive CAD. Results may question the concept of microvascular angina as currently defined.
Prevalence and distribution of peripheral musculoskeletal manifestations in spondyloarthritis including psoriatic arthritis: results of the worldwide, cross-sectional ASAS-PerSpA study
Authors: López-Medina Clementina , Molto Anna , Sieper Joachim , Duruöz Tuncay , Kiltz Uta , Elzorkany Bassel , Hajjaj-Hassouni Najia , Burgos-Vargas Ruben , Maldonado-Cocco José , Ziade Nelly , Gavali Meghna , Navarro-Compan Victoria , Luo Shue-Fen , Monti Sara , Tae-Jong Kim , Kishimoto Mitsumasa , Pimentel-Santos F M , Gu Jieruo , Schiotis Ruxandra , van Gaalen Floris A , Geher Pál , Magrey Marina , Ibáñez Vodnizza Sebastián E , Bautista-Molano Wilson , Maksymowych Walter , Machado Pedro M , Landewé Robert , van der Heijde Desirée , Dougados Maxime
Published: January 2021

Objectives

To characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world.

Methods

Cross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated.

Results

A total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%).

Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%).

Conclusion

These results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.
COVID-19 restrictions and changing sexual behaviours in HIV-negative MSM at high risk of HIV infection in London, UK
Authors: Hyndman Iain , Nugent Diarmuid , Whitlock Gary George , McOwan Alan , Girometti Nicolò
Published: January 2021

Objectives

The COVID-19 pandemic and its related restrictions have affected attendance to and delivery of UK sexual healthcare services (SHS). We surveyed the impact on sexual behaviour of men having sex with men (MSM) to inform future SHS provision.

Methods

We conducted a cross-sectional, anonymous, web-based survey among HIV-negative MSM at high risk of HIV infection who attended 56 Dean Street, a sexual health and HIV clinic. The survey was conducted over a 7-day period in August 2020. Data on sociodemographic characteristics, sexual behaviour and related mental well-being experienced during lockdown (defined as 23 March–30 June 2020) were extracted. Categorical and non-categorical variables were compared according to HIV pre-exposure prophylaxis (PrEP) use.

Results

814 MSM completed the questionnaire: 75% were PrEP users; 76% reported they have been sexually active, of which 76% reported sex outside their household. 75% reported fewer partners than prior to lockdown. Isolation/loneliness (48%) and anxiety/stress (27%) triggered sexual activity, and 73% had discussed COVID-19 transmission risks with their sexual partners. While 46% reported no change to emotions ordinarily experienced following sex, 20% reported guilt for breaching COVID-19 restrictions. 76% implemented one or more changes to their sexual behaviour, while 58% applied one or more steps to reduce COVID-19 transmission during sex. 36% accessed SHS and 30% reported difficulties in accessing testing/treatment. Of those who accessed SHS, 28% reported an STI diagnosis. PrEP users reported higher partner number, engagement in ‘chemsex’ and use of SHS than non-PrEP users.

Conclusions

COVID-19 restrictions had a considerable impact on sexual behaviour and mental well-being in our survey respondents. High rates of sexual activity and STI diagnoses were reported during lockdown. Changes to SHS provision for MSM must respond to high rates of psychological and STI-related morbidity and the challenges faced by this population in accessing services.
Penile annular and scrotal eczematoid syphilids with penile chancre redux
Authors: Wang Qi , Wu Hao , Huang Zheng , Fan Yi-Ming
Published: January 2021

We describe a 17-year-old man who developed penile annular and scrotal eczematoid syphilids with penile chancre redux. Dermoscopy showed linear-irregular and hairpin vessels with white scales in annular lesions. Histopathology displayed psoriasiform hyperplasia with perivascular lymphoplasmacytic dermal infiltrate. Rapid plasma reagin and Treponema pallidumparticle agglutination assays were positive. The lesions disappeared after intramuscular benzathine penicillin.
SES0787LS camelina
Authors: Eynck C. , Zatylny A.M. , Klein-Gebbinck H.W. , Gugel R.K. , Falk K.C.
Published: January 2021

SES0787LS is a camelina (Camelina sativa) cultivar developed at Smart Earth Camelina Corporation in Saskatoon, SK. It was developed via hybridization followed by pedigree selection. SES0787LS has significantly higher (12%) seed yield and significantly larger seeds (29.6%) than the check cultivar AAC 10CS0048 and is adapted to all soil zones of the Canadian Prairies.
Barcoding a can of worms: testing cox1 performance as a DNA barcode of Nematoda
Authors: Gonçalves Leonardo Tresoldi , Bianchi Filipe Michels , Deprá Maríndia , Calegaro-Marques Cláudia
Published: January 2021

Accurate taxonomic identifications and species delimitations are a fundamental problem in biology. The complex taxonomy of Nematoda is primarily based on morphology, which is often dubious. DNA barcoding emerged as a handy tool to identify specimens and assess diversity, but its applications in Nematoda are incipient. We evaluated cytochrome c oxidase subunit I (cox1) efficiency as a DNA barcode for nematodes scrutinising 5241 sequences retrieved from BOLD and GenBank. The samples included genera with medical, agricultural, or ecological relevance: Anguillicola, Caenorhabditis, Heterodera, Meloidogyne, Onchocerca, Strongyloides, and Trichinella. We assessed cox1 performance through barcode gap and Probability of Correct Identification (PCI) analyses, and estimated species richness through Automatic Barcode Gap Discovery (ABGD). Each genus presented distinct gap ranges, mirroring the evolutionary diversity within Nematoda. Thus, to survey the diversity of the phylum, a careful definition of thresholds for lower taxonomic levels should be considered. PCIs were around 70% for both databases, highlighting operational biases and challenges in nematode taxonomy. ABGD inferred higher richness than the taxonomic labels informed by databases. The prevalence of specimen misidentifications and dubious species delimitations emphasise the value of integrative approaches to nematode taxonomy and systematics. Overall, cox1 is a relevant tool for integrative taxonomy of nematodes.
Aerial robotic technologies for civil engineering: established and emerging practice
Authors: Freeman M.R. , Kashani M.M. , Vardanega P.J.
Published: January 2021

Aerial robotic technology has potential for use in a wide variety of civil engineering applications. Such technology potentially offers low-cost methods to replace expensive structural health monitoring activities such as visual inspection. Aerial robots also have potential uses in civil construction and for regional surveys. This paper presents the results of a review on the applications of aerial robotic technology in civil engineering. Such civil engineering applications can be classified into three broad areas: (i) monitoring and inspection of civil infrastructure; (ii) site management, robotic construction, and maintenance; and (iii) post-disaster response surveys and rapid damage assessments. The motivations for uptake of aerial robotics in the civil engineering industry generally fall into the following categories: (i) cost savings, (ii) improved measurement capability, and (iii) safety improvements. The categories of aerial robotic use in civil engineering are then classified as either “established” or “emerging” uses.
Phase transition and entropic force of de Sitter black hole in massive gravity
Authors: Ma Yubo , Zhang Yang , Zhang Lichun , Wu Liang , Gao Ying , Cao Shuo , Pan Yu
Published: January 2021

It is well known that de Sitter(dS) black holes generally have a black hole horizon and a cosmological horizon, both of which have Hawking radiation. But the radiation temperature of the two horizons is generally different, so dS black holes do not meet the requirements of thermal equilibrium stability, which brings certain difficulties to the study of the thermodynamic characteristics of black holes. In this paper, dS black hole is regarded as a thermodynamic system, and the effective thermodynamic quantities of the system are obtained. The influence of various state parameters on the effective thermodynamic quantities in the massive gravity space-time is discussed. The condition of the phase transition of the de Sitter black hole in massive gravity space-time is given. We consider that the total entropy of the dS black hole is the sum of the corresponding entropy of the two horizons plus an extra term from the correlation of the two horizons. By comparing the entropic force of interaction between black hole horizon and the cosmological horizon with Lennard-Jones force between two particles, we find that the change rule of entropic force between the two system is surprisingly the same. The research will help us to explore the real reason of accelerating expansion of the universe.
Parameter-free description of the manifold of non-degenerate density matrices
Authors: Naudts Jan
Published: January 2021

The paper gives a definition of exponential arcs in the manifold of non-degenerate density matrices and uses it as a starting point to develop a parameter-free version of non-commutative Information Geometry in the finite-dimensional case. Given the Bogoliubov metric, the m- and e-connections are each other dual. Convex potentials are introduced. They allow to introduce dual charts. Affine coordinates are introduced at the end to make the connection with the more usual approach.