bluuebunny/crossref_metadata_2025 huggingface dataset:
Deterrence and Self-Defence
Authors: Elzein Nadine
Published: July 2021

Measures aimed at general deterrence are often thought to be problematic on the basis that they violate the Kantian prohibition against sacrificing the interests of some as a means of securing a greater good. But even if this looks like a weak objection because deterrence can be justified as a form of societal self-defence, such measures may be regarded as problematic for another reason: Harming in self-defence is only justified when it’s necessary, i.e., when there are no relatively harmless alternatives. While there are few harmless ways to remove the threat posed by dangerous individuals, there are many relatively harmless methods for preventing crime. We can bracket off our preventative failings when we think of present threats, but we cannot do so when contemplating alternative preventative measures.
Yeast Ssd1 is a non-enzymatic member of the RNase II family with an alternative RNA recognition site
Authors: Bayne Rosemary A , Jayachandran Uma , Kasprowicz Aleksandra , Bresson Stefan , Tollervey David , Wallace Edward W J , Cook Atlanta G
Published: July 2021

Ssd1, a conserved fungal RNA-binding protein, is important in stress responses, cell division and virulence. Ssd1 is closely related to Dis3L2 of the RNase II family of nucleases, but lacks catalytic activity and likely suppresses translation of bound mRNAs. Previous studies identified RNA motifs enriched in Ssd1-associated transcripts, yet the sequence requirements for Ssd1 binding are not defined. Here, we identify precise binding sites of Ssd1 on RNA using in vivo cross-linking and cDNA analysis. These sites are enriched in 5′ untranslated regions of a subset of mRNAs encoding cell wall proteins. We identified a conserved bipartite motif that binds Ssd1 with high affinity in vitro. Active RNase II enzymes have a characteristic, internal RNA binding path; the Ssd1 crystal structure at 1.9 Å resolution shows that remnants of regulatory sequences block this path. Instead, RNA binding activity has relocated to a conserved patch on the surface of the protein. Structure-guided mutations of this surface prevent Ssd1 from binding RNA in vitro and phenocopy Ssd1 deletion in vivo. These studies provide a new framework for understanding the function of a pleiotropic post-transcriptional regulator of gene expression and give insights into the evolution of regulatory and binding elements in the RNase II family.
TB or not to be: what specificities and impact do antibodies have during tuberculosis?
Authors: Hermann Clemens , King Carolyn G
Published: July 2021

Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis (Mtb), is a major cause of global morbidity and mortality. The primary barrier to the development of an effective tuberculosis vaccine is our failure to fully understand the fundamental characteristics of a protective immune response. There is an increasing evidence that mobilization of antibody and B cell responses during natural Mtb infection and vaccination play a role in host protection. Several studies have assessed the levels of Mtb-specific antibodies induced during active disease as well as the potential of monoclonal antibodies to modulate bacterial growth in vitro and in vivo. A major limitation of these studies, however, is that the specific antigens capable of eliciting humoral responses are largely unknown. As a result, information about antibody dynamics and function, which might fundamentally transform our understanding of host Mtb immunity, is missing. Importantly, Mtb infection also induces the recruitment, accumulation and colocalization of B and T cells in the lung, which are positively correlated with protection in humans and animal models of disease. These ectopic lymphoid tissues generally support local germinal center reactions for the proliferation and ongoing selection of effector and memory B cells in the mucosa. Efforts to leverage such responses for human health, however, require a more complete understanding of how antibodies and B cells contribute to the local and systemic host Mtb immunity.
Entering a new academic year: the problem faced in online learning amid COVID-19 pandemic
Authors: Rosales Renniel Jayson Jacinto , Pagsuyoin Juan Carlos C
Published: July 2021

In the crisis, we are facing, the well-being of the students is given importance in their online learning. Attention has already been given as to how the school may support in making the parents mentally healthy as they assist their children in learning. The Philippines is already entering another online academic school year as part of the health and safety protocol during this pandemic. But with all the challenges experienced by the stakeholders, the education sector is also facing a problem as to the well-being of the teachers who are also struggling in this pandemic with all the changes in their routines since online learning began.
Improving outcomes for patients hospitalized with gout: a systematic review
Authors: Russell Mark D , Clarke Benjamin D , Roddy Edward , Galloway James B
Published: July 2021

Objectives

Hospital admissions for gout flares have increased dramatically in recent years, despite widely available, effective medications for the treatment and prevention of flares. We conducted a systematic review to evaluate the effectiveness and implementation of interventions in patients hospitalized for gout flares.

Methods

A search was conducted in MEDLINE, Embase and the Cochrane library, from database inception to 8 April 2021, using the terms ‘gout’ and ‘hospital’ and their synonyms. Studies were included if they evaluated the effectiveness and/or implementation of interventions during hospital admissions or emergency department attendances for gout flares. Risk of bias assessments were performed for included studies.

Results

Nineteen articles were included. Most studies were small, retrospective analyses performed in single centres, with concerns for bias. Eleven studies (including five randomized controlled trials) reported improved patient outcomes following pharmacological interventions with known efficacy in gout, including allopurinol, prednisolone, NSAIDs and anakinra. Eight studies reported improved outcomes associated with non-pharmacological interventions: inpatient rheumatology consultation and a hospital gout management protocol. No studies to date have prospectively evaluated strategies designed to prevent re-admissions of patients hospitalized for gout flares.

Conclusion

There is an urgent need for high-quality, prospective studies of strategies for improving uptake of urate-lowering therapies in hospitalized patients, incorporating prophylaxis against flares and treat-to-target optimization of serum urate levels. Such studies are essential if the epidemic of hospital admissions from this treatable condition is to be countered.
Identification of Winter Habit Bread Wheat Landraces in the National Small Grains Collection with Resistance to Emerging Stem Rust Pathogen Variants
Authors: Gordon Tyler , Jin Yue , Gale Samuel , Rouse Matthew , Stoxen Samuel , Wanyera Ruth , Macharia Godwin , Randhawa Mandeep , Bhavani Sridhar , Brown-Guedira Gina , Marshall David , Babiker Ebrahiem , Bockelman Harold , Bonman J. Michael
Published: July 2021

Wheat stem rust caused by Puccinia graminis f. sp. tritici is a widespread and recurring threat to wheat production. Emerging P. graminis f. sp. tritici variants are rapidly overcoming major gene resistance deployed in wheat cultivars and new sources of race-nonspecific resistance are urgently needed. The National Small Grains Collection (NSGC) contains thousands of wheat landrace accessions that may harbor unique and broadly effective sources of resistance to emerging P. graminis f. sp. tritici variants. All NSGC available facultative and winter-habit bread wheat landraces were tested in a field nursery in St. Paul, Minnesota, against a bulk collection of six common U.S. P. graminis f. sp. tritici races. Infection response and severity data were collected on 9,192 landrace accessions at the soft-dough stage and resistant accessions were derived from single spikes. Derived accessions were tested in St. Paul a second time to confirm resistance and in a field nursery in Njoro, Kenya against emerging races of P. graminis f. sp. tritici with virulence to many known resistance genes including Sr24, Sr31, Sr38, and SrTmp. Accessions resistant in the St. Paul field were also tested at the seedling stage with up to 13 P. graminis f. sp. tritici races, including TTKSK and TKTTF, and with 19 molecular markers linked with known stem rust resistance genes or genes associated with modern breeding practices. Forty-five accessions were resistant in both U.S. and Kenya field nurseries and lacked alleles linked with known stem rust resistance genes. Accessions with either moderate or strong resistance in the U.S. and Kenya field nurseries and with novel seedling resistance will be prioritized for further study.
Updates on interferon in juvenile dermatomyositis: pathogenesis and therapy
Authors: Kim Hanna
Published: July 2021

Purpose of review

This review provides updates regarding the role of interferon (IFN) in juvenile dermatomyositis (JDM), including comparison to interferonopathies and therapeutic implications.

Recent findings

Transcriptomic and protein-based studies in different tissues and peripheral IFN-α assessment have demonstrated the importance of the dysregulated IFN pathway in JDM. Additional studies have validated IFN-regulated gene and protein expression correlation with disease activity in blood and muscle, with potential to predict flares. Type I and II IFN both are dysregulated in peripheral blood and muscle, with more type I IFN in skin. Muscle studies connects hypoxia to IFN production and IFN to vascular dysfunction and muscle atrophy. JDM overlaps with interferonopathy phenotype and IFN signature. There are multiple case reports and case series noting decreased IFN markers and clinical improvement in refractory JDM with Janus kinase (JAK) inhibitors.

Studies confirm IFN, particularly type I and II IFN, is an important part of JDM pathogenesis by the level of dysregulation and correlation with disease activity, as well as IFN recapitulating key JDM muscle pathology. Smaller studies indicate there may be differences by myositis-specific autoantibody group, but validation is needed. JAK inhibitors are a promising therapy as they can inhibit IFN signaling, but further study is needed regarding which patients will benefit, dosing, and safety monitoring.
Esophageal Perforation After Anterior Cervical Surgery
Authors: Modi Hitesh N. , Shreshtha Utsab , Patel Udit , Kotecha Hardik , Patel Mahesh D. , Dileep Pratibha
Published: July 2021

Summary and Background:

Esophageal perforation (EP) after anterior cervical surgery is a rare but potentially life-threatening condition. EP caused by malpositioned implants in cervical spine injury with multiple comorbidities is challenging to treat simultaneously.

Study:

This was a case report study.

Purpose of Study:

The aim of this study was to present successful treatment of EP in a subluxated C5–C6 level with implant failure, infection, septicemia, and comorbidities. The aim was to emphasize the need for a multispecialty approach while treating serious complications.

Case:

A 72-year-old woman presented to the ER with a history of operated cervical spine a week ago and having breathlessness, fever, wound infection, and tracheostomy in situ. After primary investigations, the patient was initially treated in the intensive care unit, where bleeding from the tracheostomy site was noticed. Upon endoscopy, EP was diagnosed due to implant failure. She was operated for revision cervical spine surgery (drainage of pus with anterior and posterior cervical fixation) and percutaneous endoscopic gastrostomy tube insertion (esophageal diversion). On exploration of EP, a decision was made to perform conservative treatment as initial tag sutures did not hold due to infection. Postoperatively, the patient developed rectal bleed 3 times, which was ultimately treated with cecal bleed embolization. The infected cervical wound was managed with an open dressing. The patient was managed with intermittent assisted ventilation through tracheostomy postoperatively. Barium swallow at 10 weeks confirmed healing of EP and oral feed was started. Tracheostomy closure was performed once the wound had healed, and the patient was discharged with improved neurology at 12 weeks.

Conclusions:

Perioperative problems after cervical surgery such as breathing difficulty, wound discharge, and worsening of neurology may lead to suspicion of underlying EP due to implant failure. Upper gastrointestinal endoscopy needs to be considered for a prompt diagnosis. Revision spine surgery with treatment of perforation simultaneously and maintenance of enteral nutrition through a percutaneous endoscopic gastrostomy tube with a multispecialty approach is recommended for this potentially life-threatening condition.
Analysis of clinical factors associated with survival in patients with soft-tissue sarcoma receiving trabectedin
Authors: Simetić Luka , Blažičević Krešimir , Ladenhauser Tatjana , Golčić Marin , Majnarić Tea , Herceg Davorin
Published: July 2021

Soft-tissue sarcomas (STSs) are a heterogeneous group of rare malignancies. Treatment for advanced STS usually starts with anthracycline-based therapies, with no clear sequence for further treatment. A preferred option is trabectedin, especially for liposarcoma and leiomyosarcoma (L-sarcoma). However, due to severe side effects and few clinical trials, further research of the parameters affecting survival is necessary for the optimal selection of patients. We retrospectively analyzed 73 consecutive patients with STS treated with trabectedin at the University Hospital Centers at Zagreb and Osijek from 2014 to 2021. Our primary goals were evaluating factors affecting progression-free survival (PFS) and overall survival (OS). The median PFS and OS for trabectedin were 3.6 months and 13.7 months, respectively. Patients with L-sarcoma exhibited longer PFS and a trend towards longer OS compared to those with non-L-sarcoma. However, these effects were primarily a result of the myxoid liposarcoma subtype, which exhibited a median PFS of 21.1 months and a median OS of 33.3 months, both significantly longer compared to non-myxoid L-sarcoma. Additionally, patients with three or more sites of metastases exhibited shorter median PFS (3.1 months vs. 3.6 months) and OS (5.7 months vs. 23.8 months) compared to only one metastatic site. There was no correlation between the PFS values of trabectedin and pazopanib and no difference in survival, regardless of the treatment sequence. Trabectedin treatment yields the greatest survival benefit in patients with myxoid liposarcoma and low metastatic burden, whereas the additional use of pazopanib provides further clinical benefit, regardless of treatment sequence.
Pulmonary toxicity following administration of granulocyte colony-stimulating factor during chemotherapy for breast cancer: a case report and literature review
Authors: Shalata Walid , Waichenberg Lauren , Massalha Ismaell , Dudnik Yulia , Rouvinov Keren , Yakobson Alexander
Published: July 2021

In this report, we aim to present a case of pulmonary toxicity in a patient that received neoadjuvant chemotherapy treatment with doxorubicin and cyclophosphamide for triple-negative breast cancer that was followed with granulocyte colony-stimulating factor (G-CSF) for prevention neutropenia, our patient presented with chest discomfort and dyspnea, with radiologic evidence of radiologic investigations showed acute respiratory distress syndrome, after investigation and follow up we came to the conclusion that it was G-CSF adverse effect.
LMCD1 antisense RNA 1 is a newly identified long noncoding RNA
Authors: Yalman Nesil
Published: July 2021

Long noncoding RNAs (lncRNAs) are one of the interesting fields in cancer researches. LncRNAs are generally dysregulated in many diseases. LMCD1 antisense RNA 1 (LMCD1-AS1) is a newly identified lncRNA with protumorigenic functions on tumor cells. LMCD1-AS1 expression is increased in hepatocellular carcinoma (HCC). LMCD1-AS1 is a sponge of miR-106b-5p activity. LMCD1-AS1 modulates the survival of osteosarcoma via targeting miR-106b-5p. LMCD1-AS1 and Sp1 are highly expressed in osteosarcoma. SP1 can bind to the promoter region of LMCD1-AS1, resulting in its overexpression in osteosarcoma. GLI2 is shown to bind to the LMCD1-AS1 promoter and is transcriptionally activated by LMCD1-AS1. LMCD1 acts as a miR-1287-5p sponge to increase GLI2 expression. LMCD1 is abundantly expressed in kidney tissue. Moreover, it is functionally involved in protein-protein interactions with transcriptional co-repressor activity, including regulation of the calcineurin-NFAT signaling cascade known to play a critical role in recovery from acute kidney injury (AKI). The E2F1/LMCD1-AS1/miR-345-5p/COL6A3 axis is a newly identified regulatory mechanism, which has a function in cholangiocarcinoma (CCA) tumorigenesis and progression and provides potential therapeutic targets for CCA. Also, LMCD1-AS1 functions in thyroid cancer (THCA) development. LMCD1-AS1 is overexpressed in THCA cells, and LMCD1-AS1 knockdown suppresses the malignant phenotypes of THCA cells. In THCA development, LMCD1-AS1 exerts protumorigenic function through sponging miR-1287-5p to increase GLI2 expression, constituting a feedback loop of LMCD1-AS1/miR-1287-5p/GLI2. In this review, the author focuses on the molecular mechanisms of newly identified long noncoding RNA LMCD1 antisense RNA 1 (LMCD1-AS1).
High grade neuroendocrine carcinoma of the breast, first line and maintenance immunotherapy
Authors: Symeonidis David , Papageorgiou Georgios , Liatsos Alexandros , Trihia Helen , Lianos Evangelos , Kosmas Christos
Published: July 2021

Small cell carcinomas (SCCs) are poorly differentiated neuroendocrine tumors that arise predominantly in the lung and gastrointestinal tract (GIT). Neuroendocrine carcinomas can occur in a variety of extrapulmonary sites throughout the body, including breast, larynx, GIT, prostate, urinary bladder, ovary and cervix. This is a case report of a 55-year-old Asian female patient with metastatic high-grade neuroendocrine carcinoma of unknown origin that responded notably to off-label nivolumab maintenance treatment after first-line carboplatin – etoposide chemotherapy and radiation. After 2 years of nivolumab after platinum-based chemotherapy results from PET-CT showed no residual disease and we proceeded to mastectomy.
Efficacy and biomarker exploration of camrelizumab combined with apatinib in the treatment of advanced primary liver cancer: a retrospective study
Authors: Zeng Zhiming , Jiang Yanfeng , Liu Cuizhen , Zhu Guangzhi , Ma Fuchao , Yang Lihua , Qiu Jinfeng , Tang Jing , Ye Xinping , Peng Tao , Zeng Jie , Ma Jie
Published: July 2021

This study was to explore the efficacy and safety of camrelizumab combined with apatinib in patients with advanced liver cancer. Moreover, the relationship between peripheral blood parameters and tumor response rate was also investigated. Patients with unresectable or recurrent primary liver cancer (PLC) who received treatment from July 2019 to July 2020 in the First Affiliated Hospital of Guangxi Medical University were included in this single-center retrospective study. The patients were treated with camrelizumab (200 mg, intravenous q2w) plus apatinib (250 mg, oral qd) until the occurrence of disease progression or unbearable toxicity. All the patients underwent blood routine test and detection of lactate dehydrogenase and serum albumin levels before treatment. The primary endpoints were objective response rate (ORR) and disease control rate (DCR). This study included a total of 45 patients. The overall ORR was 33.3% [95% confidence interval (CI),19.0–47.7] and the overall DCR was 57.8% (95% CI, 42.8–72.8). The ORR and DCR were higher in the first-line treatment than those in the second-line treatment (ORR: 45.5% vs. 21.7%, DCR: 63.6% vs. 52.3%). Median progression-free survival in the second-line treatment was 10.5 months (95% CI, 7.9–13.1, P = 0.022). Adverse events occurred in 39 (86.7%) patients. Grade 3/4 adverse reactions occurred in 7 (15.6%) patients. One patient (4.3%) was terminated from treatment due to adverse events. One patient (4.3%) died, which was potentially associated with adverse events. Subgroup analysis indicated that the remission rate in patients with high lymphocyte to monocyte ratio (H-LMR) was higher than that in patients with low lymphocyte to monocyte ratio (L-LMR) (56.25% vs. 25.93%, P = 0.047), and the remission rate in patients with high Prognostic Nutritional Index (H-PNI) was higher than that in patients with low Prognostic Nutritional Index (L-PNI) (66.7% vs. 26.5%, P = 0.046). Camrelizumab combined with apatinib in the treatment of PLC showed encouraging clinical efficacy, with tolerable toxicities. Levels of PNI and LMR may serve as predictors of the prognosis of advanced PLC patients who receive immunotherapy combined with targeted therapy.
Long-term response to immuno-oncology after discontinuation for immuno-related pneumonia in metastatic renal carcinoma: a case report
Authors: Stellato Marco , Foderaro Simone , Tonini Giuseppe , Vincenzi Bruno , Santini Daniele
Published: July 2021

Immuno-oncology demonstrated substantial efficacy in cancer treatment. Immune-related adverse events (irAEs) can virtually involve every organ, with different incidence depending on the different immune-checkpoint inhibitor. irAEs consequences can range from quality of life worsening and therapy discontinuation to death, if not recognized promptly. However, patients interrupting therapy due to irAEs in absence of progressive disease can benefit from immuno-oncology over time after discontinuation. We present the case of a man affected by metastatic renal cell carcinoma (mRCC) that experienced a long-term response to programmed cell death-1 inhibitor, nivolumab, after interruption due to immune-related pnenumonia. IrAEs can be associated to efficacy and very long-term response in mRCC patients treated with immuno-oncology.
Large Plaque-type Blue Nevus with GNAQ Q209P Mutation, Involving Mammary Gland Tissue: Under-Recognized Mammary Condition as an Origin of Primary Mammary Melanocytic Tumors
Authors: Satake Kosuke , Sudo Tamotsu , Sugino Takashi , Yoshikawa Shusuke , Kiyohara Yoshio , Hayashi Tomomi , Nakashima Kazuaki , Goto Keisuke
Published: July 2021

Plaque-type blue nevus is a rare variant of blue nevi that was first described in 1954. This article presents clinical, macroscopic, histopathological, and genetic findings for a case of large plaque-type blue nevus expanding into the mammary gland tissue as well as the skin of the right breast. A 63-year-old woman presented with a congenital, large, blue-colored macule limited to the hypochondriac area of the right breast. A nodule 8 mm in diameter was also present in the mammary gland tissue. Magnetic resonance imaging was unable to detect diffuse melanin deposition in the mammary gland tissue, but pigmentation in the whole mammary parenchyma was observed in the cut surfaces of the mastectomy specimen. Histopathology revealed a sparse distribution of dendritic melanocytes in whole sections of the mammary fibrous tissue and partial sections of the dermis. The histopathological criteria for atypical cellular blue nevus were fulfilled for the mammary tumor. Nodal blue nevus was diagnosed in the sentinel lymph node. Sanger sequencing confirmed theGNAQQ209P mutation, which was also identified in all 4 literature cases of plaque-type blue nevus, but rarely in conventional blue nevi and uveal melanoma. It should be noted that plaque-type blue nevus can expand into the mammary gland tissue, even if the pigmented lesion does not exist on the overlying breast skin. The mammary condition can be the origin of primary mammary melanocytic tumors. Mosaicism of theGNAQQ209P mutation can be a characteristic genetic alteration to extensive blue nevi, including plaque-type blue nevus.
Optimizing Detection of Lymphatic Invasion in Primary Cutaneous Melanoma With the Use of D2-40 and a Paired Melanocytic Marker
Authors: Straker Richard J. , Taylor Laura A. , Neuwirth Madalyn G. , Sinnamon Andrew J. , Shannon Adrienne B. , Abbott James , Miura John T. , Chu Emily Y. , Xu Xiaowei , Karakousis Giorgos C.
Published: July 2021

Dual immunohistochemical (IHC) staining with D2-40 and S100 improves detection of lymphatic invasion (LI) in primary cutaneous melanoma. However, limited data exist evaluating this technique using other melanocytic markers, and thus, the optimal marker for detection of LI is unestablished. To address this knowledge gap, a case–control study was performed comparing melanoma specimens from 22 patients with known lymphatic spread (LS) with a control group of 11 patients without LS. Specimens underwent dual IHC staining with D2-40 and MART-1, SOX-10, and S100 to evaluate for LI. Receiver operating characteristic analysis was used to estimate each stain's accuracy for detection of LI. The LS group was more likely to be ≥65 years (P = 0.04), have a tumor thickness of ≥1 mm (P < 0.01), and have ulcerated tumors (P = 0.02). Detection of LI with D2-40/MART-1 significantly correlated with LS (P = 0.03), and the D2-40/MART-1 stain was most accurate for LI based on receiver operating characteristic curve analysis (area under the curve [AUC] 0.705) in comparison with D2-40/SOX-10 (AUC 0.575) and D2-40/S100 (AUC 0.633). These findings suggest that MART-1 may be the optimal melanocytic marker to combine with D2-40 for detection of LI in melanoma. Further studies are needed to determine the utility of routinely performing these stains for histopathologic analysis of melanoma.
Supine hypotensive syndrome of pregnancy
Authors: Massoth Christina , Chappell Daniel , Kranke Peter , Wenk Manuel
Published: July 2021

Since the first description of supine hypotensive syndrome in the 1950s, its potentially detrimental effects on otherwise healthy women during late pregnancy have become a persistent challenge in obstetric practice. Establishing a 15° left lateral tilt during labour and caesarean section is a fundamental principle of obstetric care, universally adopted and upheld by current guidelines and recommendations. Reassessment of the original landmark studies in the light of current physiological and anatomical knowledge questions adherence to this standard in clinical practice. The modern practice of providing vasopressor support during caesarean delivery under neuraxial anaesthesia appears to negate any potential negative effects of a maternal full supine position. Recent MRI studies provide evidence as to the cause of supine hypotension and the physiological effects of different maternal positions at term. This review highlights current data on the acute supine hypotensive syndrome in contrast to traditional knowledge and established practice.
Unusual Presentation of Extensor Tendon Rupture Caused by a Dorsal Wrist Synovial Cyst
Authors: Allahham Salim , Aljassem Ghanem , Alyazji Zaki , Sada Ruba , Abuelgasim Mutaz , Otman Sami , Albasti Habib
Published: July 2021

Synovial cysts are juxta-articular-fluid–filled collections that are lined by synovial cells, distinguishing them from a very close cystic lesion, which is the ganglion cyst. They usually present with pain and unpleasant appearance; here we present a case of wrist synovial cyst that caused extensor tendon rupture. A 50-year-old woman presented to our clinic with a cystic lesion on the dorsum of her wrist, with an inability to extend her index finger. The lesion was found intraoperatively engulfing the extensors of the index and causing a rupture. The cyst was excised and the tendon was reconstructed; pathology report confirmed the lesion as synovial cyst. Synovial cysts and ganglion cysts are two different entities but they have been used interchangeably in the literature; pathology is the only way to differentiate between them because they usually present with identical scenarios. None of them were reported to cause extensor tendon rupture, as presented in our article. Synovial cysts can cause rupture to extensor tendons if they arise from the sheath, and it is better to anticipate synovial cyst and remove it surgically before causing any further damage, if the lesion appeared to rise from the tendon sheath on further imaging.
Gaps in standards for integrating artificial intelligence technologies into ophthalmic practice
Authors: Baxter Sally L. , Lee Aaron Y.
Published: July 2021

Purpose of review

The purpose of this review is to provide an overview of healthcare standards and their relevance to multiple ophthalmic workflows, with a specific emphasis on describing gaps in standards development needed for improved integration of artificial intelligence technologies into ophthalmic practice.

Recent findings

Healthcare standards are an essential component of data exchange and critical for clinical practice, research, and public health surveillance activities. Standards enable interoperability between clinical information systems, healthcare information exchange between institutions, and clinical decision support in a complex health information technology ecosystem. There are several gaps in standards in ophthalmology, including relatively low adoption of imaging standards, lack of use cases for integrating apps providing artificial intelligence -based decision support, lack of common data models to harmonize big data repositories, and no standards regarding interfaces and algorithmic outputs.

These gaps in standards represent opportunities for future work to develop improved data flow between various elements of the digital health ecosystem. This will enable more widespread adoption and integration of artificial intelligence-based tools into clinical practice. Engagement and support from the ophthalmology community for standards development will be important for advancing this work.
Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl positron emission tomography and computed tomography
Authors: Aarnio Mikko , Fredrikson Mats , Lampa Erik , Sörensen Jens , Gordh Torsten , Linnman Clas
Published: July 2021

Knowledge of etiological mechanisms underlying whiplash-associated disorders is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in whiplash-associated disorders would facilitate diagnosis, strengthen patients' subjective pain reports, and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study, we evaluated combined [11C]-D-deprenyl positron emission tomography and computed tomography after acute whiplash injury and at 6-month follow-up. Sixteen adult patients (mean age 33 years) with whiplash injury grade II were recruited at the emergency department. [11C]-D-deprenyl positron emission tomography and computed tomography, subjective pain levels, self-rated neck disability, and active cervical range of motion were recorded within 7 days after injury and again at 6-month follow-up. Imaging results showed possible tissue injuries after acute whiplash with an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints, associated with subjective pain locale and levels, as well as self-rated disability. At follow-up, some patients had recovered and some showed persistent symptoms and reductions in [11C]-D-deprenyl uptake correlated to reductions in pain levels. These findings help identify affected peripheral structures in whiplash injury and strengthen the idea that positron emission tomography and computed tomography detectable organic lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury.
Mitochondrial calcium uniporter deletion prevents painful diabetic neuropathy by restoring mitochondrial morphology and dynamics
Authors: George Dale S. , Hackelberg Sandra , Jayaraj Nirupa D. , Ren Dongjun , Edassery Seby L. , Rathwell Craig A. , Miller Rachel E. , Malfait Anne-Marie , Savas Jeffrey N. , Miller Richard J. , Menichella Daniela M.
Published: July 2021

Painful diabetic neuropathy (PDN) is an intractable complication affecting 25% of diabetic patients. Painful diabetic neuropathy is characterized by neuropathic pain accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability, resulting in calcium overload, axonal degeneration, and loss of cutaneous innervation. The molecular pathways underlying these effects are unknown. Using high-throughput and deep-proteome profiling, we found that mitochondrial fission proteins were elevated in DRG neurons from mice with PDN induced by a high-fat diet (HFD). In vivo calcium imaging revealed increased calcium signaling in DRG nociceptors from mice with PDN. Furthermore, using electron microscopy, we showed that mitochondria in DRG nociceptors had fragmented morphology as early as 2 weeks after starting HFD, preceding the onset of mechanical allodynia and small-fiber degeneration. Moreover, preventing calcium entry into the mitochondria, by selectively deleting the mitochondrial calcium uniporter from these neurons, restored normal mitochondrial morphology, prevented axonal degeneration, and reversed mechanical allodynia in the HFD mouse model of PDN. These studies suggest a molecular cascade linking neuropathic pain to axonal degeneration in PDN. In particular, nociceptor hyperexcitability and the associated increased intracellular calcium concentrations could lead to excessive calcium entry into mitochondria mediated by the mitochondrial calcium uniporter, resulting in increased calcium-dependent mitochondrial fission and ultimately contributing to small-fiber degeneration and neuropathic pain in PDN. Hence, we propose that targeting calcium entry into nociceptor mitochondria may represent a promising effective and disease-modifying therapeutic approach for this currently intractable and widespread affliction. Moreover, these results are likely to inform studies of other neurodegenerative disease involving similar underlying events.
Effect of unfractionated heparin and low molecular weight heparin on the clotting of platelet-reduced whole blood: an in-vitro study utilizing thromboelastography
Authors: Chung Jason , Stevic Ivan , Gantioqui Jorell , Atkinson Helen , Chan Anthony K.C. , Chan Howard H.W.
Published: July 2021

Treatment of venous thromboembolism with concomitant thrombocytopenia is challenging. The platelet threshold for safe administration of anticoagulants is under debate, with minimum platelet count of 50 × 109/l being recommended as the safe cutoff. However, some evidence suggests administration of anticoagulants may still be safe at platelet levels of 30 × 109/l. Therefore, we developed an in-vitro thromboelastography (TEG) study to examine the effect of therapeutic or prophylactic levels of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) on the clotting profile of platelet-reduced whole blood. Using magnetic bead-based antibody chromatography, platelets were removed to achieve platelet-depleted blood (<10 × 109/l of platelets). Platelet-depleted blood was then mixed with whole blood to produce blood samples with platelet counts of 30 × 109, 50 × 109 and 150 × 109/l. These blood samples were incubated with therapeutic or prophylactic levels of UFH or LMWH in disposable TEG cups. Clotting was initiated with 10 mmol/l calcium and optimized tissue factor levels for each anticoagulant used (2.25 pmol/l for UFH and 2.05 pmol/l for LMWH). Clotting was monitored by TEG at 37 °C for 180 min. The following TEG parameters were evaluated: R (time to clot), maximum amplitude (strength of clot) and area under the curve in 15 min (overall speed and strength of the clot at 15 min of clotting). No statistically significant differences were observed between platelet counts of 30 × 109 and 50 × 109/l for R, maximum amplitude or area under the curve in 15 min for most of the therapeutic and prophylactic doses of UFH and LMWH tested in this study. Use of anticoagulants compromised all of the TEG parameters relative to a normal platelet count of 150 × 109/l, in a dose dependent manner. The current study demonstrates that in-vitro clotting is impaired with use and increasing doses of anticoagulants. Despite this observation, we did not observe a significant difference in clotting between platelet levels of 30 × 109 and 50 × 109/l. Overall, this work provides further insight in the debated use of anticoagulants in patients with venous thromboembolism and concomitant thrombocytopenia, and provides support for possible use of anticoagulants at lower platelet thresholds.
What can a learning healthcare system teach us about improving outcomes?
Authors: Casey Jonathan D. , Courtright Katherine R. , Rice Todd W. , Semler Matthew W.
Published: July 2021

Purpose of review

This review describes the learning healthcare system paradigm, recent examples, and future directions. Patients, clinicians, and health systems frequently encounter decisions between available treatments, technologies, and healthcare delivery methods with little or no evidence about the comparative effectiveness and safety of the available options. Learning healthcare systems endeavor to recognize such knowledge gaps, integrate comparative effectiveness research – including clinical trials – into clinical care to address the knowledge gaps, and seamlessly implement the results into practice to improve care and patient outcomes.

Recent findings

Recent studies comparing the effectiveness of diagnostic tests and treatments, using information technology to identify patients likely to experience an outcome or benefit from an intervention, and evaluating models of healthcare delivery have demonstrated how a learning healthcare system approach can reduce arbitrary variation in care, decrease cost, and improve patient outcomes.

Learning healthcare systems have the potential to answer questions of importance to patients, clinicians, and health system leaders, improve efficiency of healthcare delivery, and improve patient outcomes. Achieving this goal will require realignment of the culture around clinical care, institutional and federal investment, expanded stakeholder engagement, tailored ethical and regulatory guidance, and methodologic advances in information technology and biostatistics.
How trustworthy guidelines can impact outcomes
Authors: Rochwerg Bram , Kawano-Dourado Leticia , Qadir Nida
Published: July 2021

Purpose of review

If developed using rigorous methods and produced in a timely manner, clinical practice guidelines have the potential to improve patient outcomes. Although the COVID-19 pandemic has highlighted the challenges involved in generating reliable clinical guidance, it has also provided an opportunity to address these challenges.

Recent findings

New research addressing drugs for COVID-19 is being produced at unprecedented rates. Incorporating this new knowledge into patient care can be daunting for the average clinician. In collaboration with the BMJ and MAGIC, the WHO has developed a living guideline initiative with the goal of providing rapid and trustworthy clinical guidance in response to practice-changing evidence. As new evidence becomes available, it is incorporated into a living network meta-analysis that informs these guidelines, which are iteratively updated. Until this point, the group has generated guidelines addressing the use of corticosteroids, remdesivir, hydroxychloroquine, lopinavir/ritonavir, and ivermectin for COVID-19.

We provide an example of how rapid and rigorous guidelines can be accomplished, even in the setting of a pandemic, capitalizing on expertise, large and dedicated teams, and focused scope. We highlight the benefits of multifaceted knowledge dissemination through multiple formats to ensure global dissemination and in order to maximize impact.
Endoscopic Findings in Patients With PTEN Hamartoma Tumor Syndrome Undergoing Surveillance
Authors: Khare Anshika , Burke Carol A. , Heald Brandie , O’Malley Margaret , LaGuardia Lisa , Milicia Susan , Cruise Michael , Eng Charis , Mankaney Gautam
Published: July 2021

Goals and Background:

Phosphatase and tensin homolog hamartoma tumor syndrome (PHTS) is an inherited disorder that increases the risk for cancer in multiple organ systems, including breast, endometrial, thyroid, and the gastrointestinal tract. Surveillance is recommended however there lacks data to describe the change in polyposis phenotype and cancer incidence over surveillance. Our aim is to describe the polyposis phenotype and cancer incidence in PHTS patients undergoing endoscopic surveillance.

Study:

PHTS patients, ages 17 through 89, who underwent at least 2 esophagogastroduodenoscopy (EGDs) or colonoscopies were identified. Number and sizes of polyps were noted, from which 5 categories were recreated. Incidence of colorectal and gastric cancer was evaluated.

Results:

Seventy patients were included. Patients were clustered and classified into 1 of 5 categories: no polyps, few small polyps (<1 cm, < 10 polyps), few large polyps (≥1 cm, < 10 polyps), many small polyps (<1 cm, ≥10 polyps), many large polyps (≥1 cm, ≥10 polyps). There was no significant difference in polyp number or size on EGD (P=0.47 and 0.83, respectively) or colonoscopy (P=0.49 and 0.10, respectively) over the surveillance period (4.8±3.9 y for stomach and 5.6±4.4 y for colon). The average interval between endoscopies was 28±24 months for EGDs and 29±23 months for colonoscopies. A stage II transverse colon adenocarcinoma and stage IV gastric adenocarcinoma were identified. Standardized incidence rates for gastric and colon cancers were 5427 (P=0.0002) and 353 (P=0.002), respectively.

Conclusions:

PTHS individuals can be classified into polyposis phenotypes which do not change over an endoscopic surveillance period. Two cancers were associated with a large size polyp phenotype. Surveillance intervals should be determined by polyp size ≥1 cm and pathology.
Sarcoidosis and maligancy: the chicken and the egg?
Authors: Bonifazi Martina , Renzoni Elisabetta A. , Lower Elyse E.
Published: July 2021

Purpose of review

There is a complex interaction between sarcoidosis and malignancy. Since tumors can elicit a granulomatous reaction, the presence of granulomas alone is insufficient to diagnose sarcoidosis in a patient with cancer. In addition, check point inhibitors can also lead to a granulomatous reaction which can be misdiagnosed as sarcoidosis. These issues need to be considered when exploring the relationship between sarcoidosis and malignancy. Despite these limitations, a growing amount of evidence supports the potential interaction of sarcoidosis and malignancy.

Recent findings

Several large epidemiologic studies of patients from Europe, the USA, and Japan reveal an increased relative risk for cancer in sarcoidosis patients. The highest relative risks are seen in patients with lymphoma and breast cancer. New criteria have been developed to standardize the diagnosis of sarcoidosis, which should further clarify the association.

The diagnosis of sarcoidosis may precede or occur after malignancy. In a sarcoidosis patient with an atypical lesion, such as a breast mass, a biopsy should be considered.
Psychological factors to predict chronic diarrhea and constipation in Korean high school students
Authors: Kim Ji Young , Lim Myung Ho
Published: July 2021

Chronic diarrhea and constipation are common in adolescents and are associated with depression and anxiety. However, the association was not reported in adolescents adjusted for other psychological factors (resilience, personality traits, perceived stress, and suicidal ideation). Therefore, we investigated the significant psychological factors predicting chronic diarrhea and constipation in adjusted individuals for co-variables.

A total of 819 Korean high school students who completed bowel health and psychological questionnaires were enrolled in this study. Depression and anxiety were assessed using validated questionnaires. We used multivariate analyses, controlling for demographic, dietary, lifestyle, and psychological variables to predict chronic diarrhea and constipation.

Chronic diarrhea and constipation were more common in individuals with depression (22.3% and 18.6%, respectively) than in individuals with no depression (7.0% and 10.9%, respectively). In addition, they were more prevalent in individuals with anxiety (24.5% and 18.6%, respectively) than in individuals with no anxiety (9.1% and 12.7%, respectively). Multivariate analyses showed that resilience (adjusted risk ratio [aRR] = 0.98, adjusted 95% confidence interval [CI] = 0.97–0.99), moderate (aRR = 6.77, adjusted 95% CI = 3.55–12.91), and severe depression (aRR = 7.42, adjusted 95% CI = 3.61–15.27) were associated with chronic diarrhea. Only mild depression was associated with chronic constipation (aRR = 2.14, adjusted 95% CI = 1.36–3.38). However, anxiety was not significantly associated with chronic diarrhea or constipation.

Among the psychological factors predicting disordered bowel habits, resilience and moderate and severe depression were significant predictors of chronic diarrhea, but not anxiety. Furthermore, only mild depression was an independent predictor of chronic constipation.
Aristolochic acid nephropathy
Authors: Ji Hongjian , Hu Jingyin , Zhang Guozhe , Song Jianxiang , Zhou Xiaohua , Guo Dean
Published: July 2021

Background:

Aristolochic acid nephropathy (AAN) is a type of drug-induced nephropathy that may result in acute kidney injury and is associated with a potentially progressive course of kidney fibrosis and upper tract urothelial carcinoma. Aristolochic acids (AAs) are a group of toxins commonly present in plants of the genera Aristolochia and Asarum, which are found worldwide. AAN still occurs in Asian and Balkan regions. The progressive lesions and mutational events initiated by AAs are irreversible, and no effective therapeutic regimen for AAN has been established. Furthermore, more people are at risk of this disease due to casual exposure to AAs. This study performed a scientometric analysis of global research literature focusing on AAN.

Methods:

The Web of Science database was searched to identify all publications pertaining to “aristolochic acid nephropathy” or “Balkan endemic nephropathy” using these terms as key words to search the literature from 1971 to 2019. The collected data included the document type, author, journal, publication year, citation reports, and country of publication, and were analyzed using the VOSviewer software.

Results:

A total of 1251 records were initially obtained. Publication types, including “meeting abstract,” “letter,” “editorial material,” and “proceedings paper” were excluded, which left 1083 publications comprising 923 articles and 160 reviews. English was the predominant language of the publications. China had the most number of articles published with 217 (20.0%), followed by the USA with 186 articles (17.2%), and Germany with 138 articles (12.7%). Kidney International, Food and Chemical Toxicology, and Toxins were the 3 most active journals in publishing articles related to AAN. The total number of citations received by all publications was 39,970, with an average of 36.91 citations per article (range: 0–1769). The literature mainly focused on apoptosis, oxidative stress, and inflammation in AAN.

Conclusion:

This study indicated that AAN is a significant topic in nephrology research, as shown by the large number of publications. The literature has mainly focused on the mechanisms of AA-induced nephropathy.