bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncommon presentation of brown tumours revealing hyperparathyroidism: Three case reports
Authors: Kaouther Maatallah , Yasmine Makhlouf , Skander Kedous , Kaffel Dhia , Hanene Ferjani , Wafa Triki , Dorra Ben Nessib , Wafa Hamdi 
Published: March 2022

ABSTRACT
Brown tumours (BTs) are focal bone lesions encountered in patients with uncontrolled hyperparathyroidism (HPT). They are due to a proliferation of multinucleated giant cells in osteolytic lesions. Because of early screening of bone metabolism disorders, BTs are rare bone manifestations. More importantly, they scarcely reveal the disease. We demonstrate through these two cases reports unusual locations of BT complicating the course of HPT due to parathyroid hyperplasia.
Noninvasive Testing and Surrogate Markers in Invasive Fungal Diseases
Authors: Thompson George R , Boulware David R , Bahr Nathan C , Clancy Cornelius J , Harrison Thomas S , Kauffman Carol A , Le Thuy , Miceli Marisa H , Mylonakis Eleftherios , Nguyen M Hong , Ostrosky-Zeichner Luis , Patterson Thomas F , Perfect John R , Spec Andrej , Kontoyiannis Dimitrios P , Pappas Peter G 
Published: March 2022

Abstract
Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these surrogate biomarkers in this review and provide recommendations for clinicians and regulatory authorities.
Co-option of the SHOOT MERISTEMLESS network regulates protocorm-like body development in Phalaenopsis aphrodite
Authors: Fang Su-Chiung , Chen Jhun-Chen , Chang Pou-Yi , Lin Hsiang-Yin 
Published: March 2022

Abstract
The protocorm is a structure that is formed upon germination of an orchid seed. It lacks cotyledons and is ovoid in shape. The protocorm-like body (PLB), on the other hand, is a protocorm-like organ induced from somatic tissues. PLBs have been widely used for orchid micropropagation. Because of its unique structure and its application in the orchid industry, PLB development has drawn considerable interest from orchid and developmental biologists. Our previous genome-wide comparative transcriptome study demonstrated that protocorms and PLBs share similar molecular signatures and suggested that SHOOT MERISTEMLESS (STM)-dependent organogenesis is important for PLB development. Here, we show that overexpression of Phalaenopsis aphrodite STM (PaSTM) greatly enhances PLB regeneration from vegetative tissue-based explants of Phalaenopsis orchids, confirming its regulatory role in PLB development. Expression of PaSTM restored shoot meristem function of the Arabidopsis (Arabidopsis thaliana) stm-2 mutant. Moreover, we identified class S11 MYB transcription factors (TFs) as targets downstream of PaSTM. A cis-acting element, TTGACT, identified in the promoters of S11 MYB TFs was found to be important for PaSTM binding and activation. Overexpression of PaSTM or its downstream targets, PaMYB13, PaMYB14, and PaMYB17, enhanced de novo shoot regeneration in Arabidopsis, indicating the active role of the PaSTM-S11 PaMYB module in organogenesis. In summary, our data demonstrate that PaSTM is important for PLB development. The STM-S11 MYB regulatory module is evolutionarily conserved and may regulate shoot or shoot-related organ development in plants.
Clinical worsening following discontinuation of tocilizumab in diffuse cutaneous systemic sclerosis: a single-centre experience in Japan
Authors: Isomura Yohei , Shirai Yuichiro , Kuwana Masataka 
Published: March 2022

Abstract

Objective
To investigate outcomes following the tapering or discontinuation of tocilizumab in patients with diffuse cutaneous SSc (dcSSc) in a real-world setting.

Methods
Fifteen patients who were treated with tocilizumab for dcSSc were selected from a single-centre cohort database and were evaluated for serial changes in the modified Rodnan total skin thickness score (mRSS) and predicted forced vital capacity (FVC) and the occurrence of clinical worsening events after the introduction of tocilizumab.

Results
Over 12 months of treatment with tocilizumab, the mRSS decreased from 20.4 ± 10.7 to 12.3 ± 8.5 (P = 0.003) and FVC increased from 84.3 ± 13.7% to 88.5 ± 16.4% (P = 0.04). Tocilizumab was tapered or discontinued in seven and three patients, respectively, after improvement in skin thickening without occurrence or progression of organ manifestations. One (14%) of seven patients who underwent tocilizumab tapering experienced a worsening of skin thickening, while all three patients who discontinued tocilizumab experienced a worsening of skin thickening and/or new development of pericarditis, arthritis, interstitial lung disease or pulmonary arterial hypertension. The additional patient who discontinued tocilizumab due to an adverse event experienced subsequent progression of multiple organ manifestations, including skin, lung, lower gastrointestinal and renal involvement, leading to mortality.

Conclusion
Our findings suggest potential benefits of prolonged tocilizumab use in dcSSc patients. The discontinuation of tocilizumab can lead to the progression of skin and visceral manifestations. Tapering rather than the discontinuation of tocilizumab is a viable option in dcSSc patients who experience remarkable clinical improvement.
The role of comorbidities alongside patient and disease characteristics in long-term disease activity in RA using UK inception cohort data
Authors: Busby Amanda D , Wason James , Pratt Arthur G , Young Adam , Isaacs John D , Nikiphorou Elena 
Published: March 2022

Abstract

Objectives
Control of disease activity in RA is a crucial part of its management to prevent long-term joint damage and disability. This study aimed to identify early predictors of poor disease activity at 5 and 10 years, focusing on comorbidities and clinical/sociodemographic factors at first presentation.

Methods
Patients from two UK-based RA cohorts were classified into two groups; low (&lt;3.2) and moderate/high (≥3.2) DAS using 28 joint counts (DAS28) at 5/10 years. Clinical variables (e.g. rheumatoid nodules, erosions), sociodemographic factors (e.g. ethnicity, deprivation) and comorbidities were recorded at baseline and yearly thereafter. The Rheumatic Diseases Comorbidity Index quantified patient comorbidity burden. Binary logistic regression models (outcome low vs moderate/high DAS28) were fitted using multiple imputation.

Results
A total of 2701 patients living with RA were recruited (mean age 56.1 years, 66.9% female); 5-year data were available for 1718 (63.4%) patients and 10-year data for 820 (30.4%). Baseline Rheumatic Diseases Comorbidity Index was not associated with DAS28 at 5 [odds ratio (OR) 1.05, 95% CI 0.91, 1.22] or 10 years (OR 0.99, 95% CI 0.75, 1.31) in multivariable analyses. Sociodemographic factors (female gender, worse deprivation) and poorer baseline HAQ-Disability Index were associated with DAS28 ≥3.2 at both timepoints. Being seropositive was associated with 5-year DAS28 ≥3.2.

Conclusion
This study demonstrates an association between sociodemographic and clinical factors and long-term RA disease activity, in models adjusting for comorbidity burden. The findings call for more holistic and targeted patient management in patients with RA and provide insights for more individualized management plans even on first presentation to rheumatology.
Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II)
Authors: Lynggaard Charlotte Duch , Grønhøj Christian , Christensen Robin , Fischer-Nielsen Anne , Melchiors Jacob , Specht Lena , Andersen Elo , Mortensen Jann , Oturai Peter , Barfod Gry Hoffmann , Haastrup Eva Kannik , Møller-Hansen Michael , Haack-Sørensen Mandana , Ekblond Annette , Kastrup Jens , Jensen Siri Beier , von Buchwald Christian 
Published: March 2022

Abstract
No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC)—xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL/minute at baseline to 0.18 mL/minute with a change of 0.06 (P = .0009) mL/minute. SWS flow rate increased from 0.66 mL/minute at baseline to 0.75 mL/minute with a change of 0.09 (P = .017) mL/minute. XQ summary score decreased by 22.6 units (P = .0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26.7 (P = .0013), sticky saliva 23.3 (P = .0015), and swallowing 10.0 (P = .0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.
Explaining Racial-ethnic Disparities in the Receipt of Medication for Opioid Use Disorder during Pregnancy
Authors: Gao Yitong Alice , Drake Coleman , Krans Elizabeth E. , Chen Qingwen , Jarlenski Marian P. 
Published: March 2022

Objective
Factors contributing to racial and ethnic disparities in medication for opioid use disorder (MOUD) receipt during pregnancy are largely unknown. We quantified the contribution of individual, healthcare access and quality, and community factors to racial-ethnic disparities in MOUD during pregnancy and postpartum among Medicaid-enrolled pregnant women with opioid use disorder (OUD).

Methods
This retrospective cohort study used regression and nonlinear decomposition to examine how individual, healthcare access and quality, and community factors explain racial-ethnic disparities in MOUD receipt among Medicaid-enrolled women with OUD who had a live birth from 2011 to 2017. The exposure was self-reported race and ethnicity. The outcomes were any MOUD receipt during pregnancy or postpartum. All factors included were identified from the literature.

Results
Racial-ethnic disparities in individual, healthcare access and quality, and community factors explained 15.8% of the racial-ethnic disparity in MOUD receipt during pregnancy and 68.9% of the disparity in the postpartum period. Despite comparable healthcare utilization, non-White/Hispanic women were diagnosed with OUD 37 days later in pregnancy, on average, than non-Hispanic White women, which was the largest contributor to the racial-ethnic disparity in MOUD receipt during pregnancy (111.0%). The racial-ethnic disparity in MOUD receipt during pregnancy was the largest contributor (112.2%) to the racial-ethnic disparity in MOUD in the postpartum period.

Conclusions
Later diagnosis of OUD in pregnancy among non-White/Hispanic women partially explains the disparities in MOUD receipt in this population. Universal substance use screening earlier in pregnancy, combined with connecting patients to evidence-based and culturally competent care, is one approach that could close the observed racial-ethnic disparity in MOUD receipt.
Patient Harm and Institutional Avoidability of Out-of-Hours Discharge From Intensive Care: An Analysis Using Mixed Methods*
Authors: Vollam Sarah , Gustafson Owen , Morgan Lauren , Pattison Natalie , Thomas Hilary , Watkinson Peter 
Published: March 2022

OBJECTIVES:
Out-of-hours discharge from ICU to the ward is associated with increased in-hospital mortality and ICU readmission. Little is known about why this occurs. We map the discharge process and describe the consequences of out-of-hours discharge to inform practice changes to reduce the impact of discharge at night.

DESIGN:
This study was part of the REcovery FoLlowing intensive CarE Treatment mixed methods study. We defined out-of-hours discharge as 16:00 to 07:59 hours. We undertook 20 in-depth case record reviews where in-hospital death after ICU discharge had been judged “probably avoidable” in previous retrospective structured judgment reviews, and 20 where patients survived. We conducted semistructured interviews with 55 patients, family members, and staff with experience of ICU discharge processes. These, along with a stakeholder focus group, informed ICU discharge process mapping using the human factors–based functional analysis resonance method.

SETTING:
Three U.K. National Health Service hospitals, chosen to represent different hospital settings.

SUBJECTS:
Patients discharged from ICU, their families, and staff involved in their care.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Out-of-hours discharge was common. Patients and staff described out-of-hours discharge as unsafe due to a reduction in staffing and skill mix at night. Patients discharged out-of-hours were commonly discharged prematurely, had inadequate handover, were physiologically unstable, and did not have deterioration recognized or escalated appropriately. We identified five interdependent function keys to facilitating timely ICU discharge: multidisciplinary team decision for discharge, patient prepared for discharge, bed meeting, bed manager allocation of beds, and ward bed made available.

CONCLUSIONS:
We identified significant limitations in out-of-hours care provision following overnight discharge from ICU. Transfer to the ward before 16:00 should be facilitated where possible. Our work highlights changes to help make day time discharge more likely. Where discharge after 16:00 is unavoidable, support systems should be implemented to ensure the safety of patients discharged from ICU at night.
Role of epigenetic abnormalities and intervention in obstructive sleep apnea target organs
Authors: Ou Yanru , Zong Dandan , Ouyang Ruoyun 
Published: March 2022

Abstract
Obstructive sleep apnea (OSA) is a common condition that has considerable impacts on human health. Epigenetics has become a rapidly developing and exciting area in biology, and it is defined as heritable alterations in gene expression and has regulatory effects on disease progression. However, the published literature that is integrating both of them is not sufficient. The purpose of this article is to explore the relationship between OSA and epigenetics and to offer better diagnostic methods and treatment options. Epigenetic modifications mainly manifest as post-translational modifications in DNA and histone proteins and regulation of non-coding RNAs. Chronic intermittent hypoxia-mediated epigenetic alterations are involved in the progression of OSA and diverse multiorgan injuries, including cardiovascular disease, metabolic disorders, pulmonary hypertension, neural dysfunction, and even tumors. This article provides deeper insights into the disease mechanism of OSA and potential applications of targeted diagnosis, treatment, and prognosis in OSA complications.
The prevalence and outcomes of α- and β-thalassemia among pregnant women in Hubei Province, Central China
Authors: Cheng Yao , Chen Miaomiao , Ye Jiazhi , Yang Qin , Wang Ronggui , Liu Shulian , Su Rui , Song Jieping , Gao Tangxinzi , Xu Runhong , Zhao Feixia , Zhang Peili , Sun Guoqiang 
Published: March 2022

Abstract
There is no information concerning the prevalence of thalassemia among pregnant women in Hubei Province currently. This study is aimed to explore the prevalence of α- and β-thalassemia genotypes among pregnant women in Hubei Province, and to explore the clinically applicable screening approach, as well as to investigate the pregnancy outcomes of α- and β-thalassemia carriers.
Pregnant participants were recruited from 4 hospitals for the screening of α- and β-thalassemia mutations in Hubei Province. Polymerase Chain Reaction and flow cytometry methods were used to examine α- and β-thalassemia mutations. The hematological parameters and pregnancy outcomes of α- and β-thalassemia carriers were obtained from the hospital information system. The chi-square tests were used to evaluate the difference in hematological parameters between pregnant thalassemia carriers and the control group.
Among 11,875 participants, 414 (3.49%) were confirmed with α-thalassemia carriers, 228 (1.92%) were confirmed with β-thalassemia carriers, and 3 (0.03%) were confirmed with both α- and β-thalassemia carriers. The frequency of –α3.7 accounted for 2.05% and it was the most frequent genotype of α-thalassemia; the proportion of IVS-II-654 was 0.85% and it was the most frequent genotype of β-thalassemia in Hubei Province. Furthermore, the proportion of patients with low mean corpuscular volume (MCV) or mean cell hemoglobin (MCH) values was accounted for 36.64% and 93.97% among α-thalassemia and β-thalassemia carriers, respectively. And participants with normal MCV and MCH values were accounted for 95.07% among non-thalassemia participants. High prevalence of pregnancy-induced diabetes (16.97%), preterm birth (9.96%), pregnancy-induced hypertension (8.12%), and low birth weight (5.90%) were observed among pregnant thalassemia carriers.
MCV and MCH values were suggested to apply on the preliminary screening of pregnant β-thalassemia; however, it's unpractical on that of α-thalassemia. Furthermore, thalassemia carriers might have a high risk of negative pregnancy outcomes. These findings could be useful for the preliminary screening of thalassemia and perinatal care for the pregnant thalassemia carriers.
Intracranial Epstein-Barr virus-associated smooth muscle tumor with superimposed cryptococcal infection
Authors: Barrett Kaylyn , Tavakoli Sam , McGinity Michael , Gilbert Andrea 
Published: March 2022

Abstract

Rationale:
Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) are rare, virally-induced malignancies that occur almost exclusively in immunocompromised individuals. We report a very rare case of a dura-based EBV-SMT with superimposed local cryptococcal infection.

Patient concerns:
An adult male with a history of untreated acquired immunodeficiency syndrome presented to our hospital with worsening headaches, diarrhea, and diffuse myalgias.

Diagnoses:
Blood cultures were positive for methicillin-resistant Staphylococcus aureus and Cryptococcus neoformans serum antigen. Magnetic resonance imaging revealed 2 adjacent enhancing masses in the right temporal lobe, perilesional edema, and mass effect of the right lateral ventricle. Histological examination and immunohistochemical stains of the surgical specimen were consistent with EBV-SMT. Cryptococcus organisms were identified within the neoplasm.

Interventions:
The patient underwent complete tumor resection, received an extended course of amphotericin and flucytosine, and was restarted on antiretroviral therapy.

Outcomes:
The patient was discharged from the hospital with no focal neurological deficits.

Lessons:
Epstein-Barr virus associated smooth muscle tumors are rare malignancies that occur in immunocompromised patients. Prognosis is largely dependent on immune reconstitution and treatment of concomitant infections.
Normal pressure hydrocephalus
Authors: Micchia Katia , Formica Caterina , De Salvo Simona , Muscarà Nunzio , Bramanti Placido , Caminiti Fabrizia , Marino Silvia , Corallo Francesco 
Published: March 2022

Abstract
Idiopathic normal pressure hydrocephalus (NPH) is a syndrome that affects elderly people and is characterized by excessive accumulation of cerebrospinal fluid in the brain ventricles. Diagnosis is based on the evaluation of clinical symptoms, which consists of a classic triad (Hakim triad), gait disturbances, cognitive impairment, and urinary incontinence. However, this complete triad is not always seen; therefore, it is difficult to make the diagnosis. NPH can be divided into primary or idiopathic NPH and secondary NPH. Diagnostic criteria for NPH remain a topic of discussion; however, the development of diagnostic techniques has brought new opportunities for diagnosis. The aim of this review is to present an overview of neurophysiological and neuropsychological approaches to support the clinical evaluation of patients with NPH and contribute to the differential diagnosis of NPH and dementia, as the clinical symptoms of NPH may resemble other neurodegenerative disorders.
Treatment of refractory MALT lymphoma by lenalidomide plus bendamustine
Authors: Zhou Zhencang , Wu Pengqiang , Wang Fujue , Tao Huan , Chen Yingying , Gao Jie , Chen Dengke , Jia Yongqian 
Published: March 2022

Abstract

Rationale:
Marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) has an indolent natural course and disseminates slowly. However, there is currently no consensus regarding the optimal treatment strategy for relapsed/refractory MALT lymphomas. Lenalidomide-bendamustine may be an effective regimen for such cases.

Patient concerns:
A 48-year-old Chinese male patient with MALT lymphoma and API2/MALT received 2 courses of standard-dose rituximab, cyclophosphamide, vincristine, prednisone regimen chemotherapy combined with Helicobacter pylori eradication therapy. However, this disease was not effectively managed.

Diagnosis:
MALT lymphoma.

Interventions:
The patient received lenalidomide-bendamustine (lenalidomide 25 mg on days 1–21 and bendamustine 90 mg/m2 on days 1–2) for 6 courses.

Outcomes:
Lenalidomide-bendamustine was a safe and effective chemotherapy. No serious adverse events occurred during the treatment period. Ultrasound gastroscopy revealed that the tumor gradually shrank and eventually disappeared to complete remission.

Lessons:
The lenalidomide-bendamustine scheme might be a potentially effective option for patients with refractory or relapsed MALT lymphoma.