bluuebunny/crossref_metadata_2025 huggingface dataset:
The appropriate number of preoperative core needle biopsy specimens for analysis in breast cancer
Authors: Sun Tao , Zhang Hanwen , Gao Wei , Yang Qifeng
Published: April 2021

Ultrasound (US)-guided core needle biopsy (CNB) has been recognized as a crucial diagnostic tool for breast cancer. However, there is a lack of guidance for hospitals that are not equipped with adjunctive US. The aim of this study was to assess the sensitivity, specificity, and experience of freehanded CNB in the outpatient department, and to determine the minimum number of tissue strips required to obtain concordance for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and tumor grade with the excised specimen.

A prospective study was performed on 95 patients undergoing CNB and subsequent surgical procedures. The reliability of immunohistochemical assessments of the pathological type, tumor grade, ER, PR, and HER2 status in CNBs was compared with that of surgical specimens. Concordance between the CNBs and surgical samples was estimated as a percentage agreement, and analyzed using the chi-square test. A P < .05 was considered significant.

The concordance rates of ER, PR, and HER2 status and tumor grade status between CNBs and surgically excised specimens were 97.9%, 91.6%, 82.1%, and 84.2%, respectively. The reliability of taking 2 tissue strips was similar to that of taking six tissue strips in distinguishing malignancy from benignancy, and determining the pathological type without the aid of US. Four tissue strips obtained by CNB showed good accuracy comparable to those obtained by surgical specimens in assessing ER, PR, and HER2 status and tumor grade.

Two tissue strips obtained by CNB showed good accuracy in differentiating malignancy from benignancy, while at least 4 strips are recommended to obtain overall conformity of pathological biomarkers.
Efficacy and safety of methylprednisolone against acute respiratory distress syndrome
Authors: Lv Hai , Dai Linfeng , Lu Jun , Cheng Lu , Geng Yanxia , Chen Mingqi , Chen Qiuhua , Wang Xing
Published: April 2021

Background:

Acute respiratory distress syndrome (ARDS) is caused by an inflammatory injury to the lung. Dysregulated inflammation is the cardinal feature of ARDS. Methylprednisolone is an option for treating ARDS. However, the benefits and adverse effects of methylprednisolone have not been well assessed in patients with ARDS. This study aimed to evaluate the efficacy and safety of methylprednisolone against ARDS.

Material and methods:

The electronic database of Embase, PubMed, the Cochrane Library, CNKI, and Wanfang were searched, and randomized controlled trials (RCTs) reporting the efficacy and safety of methylprednisolone for ARDS were included. Revman 5.3 and Stata 15.0 were used to conduct the analysis. The fixed-effects model was used to calculate summary odds ratios (ORs) and 95% confidence interval (CIs).

Results:

Ten RCTs studies involving 692 patients with ARDS. The summary results demonstrated that, compared with placebo, methylprednisolone had a statistically significant effect on mortality (OR = 0.64; 95% CI: 0.43–0.95, I

2
 = 42%); the time of mechanical ventilation (MD) = –2.70, 95% CI: –3.31 to –2.10; I
2 = 0%) in patients with ARDS, but it was not associated with increased rates of adverse events (OR = 0.80; 95% CI: 0.34–1.86; I
2 = 58%).

Conclusions:

This systematic review and meta-analysis demonstrated that Methylprednisolone is safe against ARDS. It may reduce mortality and shorten the time of mechanical ventilation. However, well-designed and large-sample studies were required to fully characterize the efficacy and safety of methylprednisolone against ARDS.
The efficacy of biomarkers in the diagnosis of acute kidney injury secondary to liver cirrhosis
Authors: Yang Yuwei , Ge Bin , Liu Yan , Feng Jiafu
Published: April 2021

This study is to investigate the role of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and creatinine in the diagnosis of acute kidney injury (AKI) secondary to liver cirrhosis.

A total of 825 patients (including 540 liver cirrhosis patients and 285 healthy controls) were enrolled. Liver cirrhosis patients were further subdivided into AKI secondary to liver cirrhosis group (AKI group, 210 patients) and simple liver cirrhosis group (LC group, 330 patients). Serum NGAL/urine NGAL (sNGAL/uNGAL), and serum creatinine (sCr) levels as well as estimated glomerular filtration rates were measured. The diagnostic performances of these indicators in AKI secondary to liver cirrhosis were evaluated.

The levels of sNGAL, uNGAL, CysC and sCr in the AKI group were significantly higher than those of LC and healthy control groups. However, the eGFR and c-aGFR of AKI group were significantly lower. With the progression of AKI (AKI-S1→AKI-S2→AKI-S3), the levels of sNGAL, uNGAL, CysC and sCr increased gradually, while the levels of c-aGFR and eGFR decreased gradually. The sNGAL, uNGAL and CysC were positively correlated with sCr (r = 0.638, 0.635, and 0.650), but negatively correlated with c-aGFR (r = -0.617, -0.606 and -0.655). However, eGFR had a negative correlation with sCr (r = -0.711), but a positive correlation with c-aGFR (r = 0.736). ROC curve analysis showed that the area under the curve for uNGAL was the largest (0.976), followed by sNGAL (0.967). The diagnostic efficacy of uNGAL and sNGAL in AKI group were 0.907 and 0.870, and the risk degrees were OR = 54.524 and 5.115, respectively.

NGAL might perform better than sCr and CysC in the diagnosis of AKI secondary to liver cirrhosis, while uNGAL might be a better indicator than sNGAL in AKI diagnosis.
Effects of functional movement screen training in high-school baseball players
Authors: Suzuki Kenta , Akasaka Kiyokazu , Otsudo Takahiro , Sawada Yutaka , Hattori Hiroshi , Hasebe Yuki , Mizoguchi Yasuaki , Hall Toby M. , Yamamoto Mitsuru
Published: April 2021

Background:

In recent years, the functional movement screen (FMS) and FMS training have attracted attention as a means of preventing injury, but no studies have examined the effect of such training in high-school baseball players. The aim of this study was to clarify the effect of FMS training on FMS score, physical function and baseball performance in high-school baseball players.

Methods:

Subjects in this randomized controlled clinical trial were high-school male baseball players assigned to either an FMS training group (intervention group) or a control group. The intervention group performed FMS training 4 times per week for 12 weeks. FMS ability, physical function, and baseball performance were measured prior to the intervention, 8, 12, and 24 weeks after the intervention in the subjects’ school environment.

Results:

A total of 71 baseball players aged 15 to 17 years were recruited and assigned to either an intervention group (n = 37) or control group (n = 34). There was no significant difference in the characteristics of participants between the 2 groups. Most FMS scores improved to 12 weeks after continued training. In the intervention group compared with the control group, deep squat, hurdle step, inline lunge, active straight leg raise, trunk stability push-up and rotary stability FMS score, total FMS score and eyes closed single leg stance time significantly increased after 8 weeks of training. While hurdle step, inline lunge, active straight leg raise, trunk stability push-up, total FMS score, and eyes closed single leg stance time significantly increased, pitching ball speed significantly decreased at the end of the 12 week training period. Eyes closed single leg stance time and feeling of fatigue significantly improved 12 weeks after training. The number of subjects who scored less than 14 for the total FMS score in the intervention group compared with control group were significantly less after 8 and 12 weeks of FMS training.

Conclusion:

FMS training for 8 weeks contributes to improving FMS scores for high-school baseball players, but FMS scores go down if FMS training is not continued.

Trial registration:

University Hospital Medical Information Network Center, Tokyo, Japan: UMIN000027553. Registered on May 30, 2017.
Efficacy and safety of colchicine in the treatment of acute myocardial infarction
Authors: Xiong Hui , Huang Xianli , Rao Lingzhang , Zhao Jinhe
Published: April 2021

Background:

There are no meta-analyses evaluating the efficacy and safety of colchicine in the treatment of acute myocardial infarction (AMI). Our protocol is conceived to evaluate the efficacy and safety of colchicine in comparison of placebo and test the hypothesis that a short course of treatment with colchicine could lead to reduced infarct size in patients presenting with AMI.

Methods:

We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines and the recommendations of the Cochrane Collaboration to conduct this meta-analysis. Reviewers will search the PubMed, Cochrane Library, Web of Science, and EMBASE online databases for all English-language cohort studies published up to April, 2021. The cohort studies focusing on assess the efficacy and safety of colchicine in the treatment of AMI will be included in our meta-analysis. At least one of the following outcomes should have been measured: reduced infarct size, C-reactive protein (CRP) level, adverse events, death and major cardiovascular events. Review Manager software will be used for the meta-analysis. All outcomes are pooled on random-effect model. A P value of <.05 is considered to be statistically significant.

Results:

Our protocol is conceived to evaluate the efficacy and safety of colchicine in comparison of placebo and test the hypothesis that a short course of treatment with colchicine could lead to reduced infarct size in patients presenting with AMI.

Registration number:

10.17605/OSF.IO/NTU5F.
The synergistic effects of applying pulsed radiofrequency lesioning of the suprascapular nerve plus physical therapy on pain and function in patients with adhesive capsulitis
Authors: Liao Weifeng , He Xinning , Du Zhiyong , Long Yi
Published: April 2021

Background:

To our knowledge, there have been no published clinical trials to assess the synergistic effects of applying pulsed radiofrequency (PRF) stimulation of the suprascapular nerve (SSN) plus physical therapy on pain and function in patients with adhesive capsulitis. Therefore, we will conduct this present randomized, double-blind study to evaluate the synergistic effects of applying PRF stimulation of the SSN plus physical therapy on pain and function in patients with adhesive capsulitis.

Methods:

The study protocol is a randomized, controlled, double-blind design. Recruitment will be started in March 2021 and completed in October 2022. The treating surgeon will assess 90 patients for eligibility. The study protocol was approved through Institutional Review Board in the People's Hospital of Beilun district of Ningbo. Each patient will be randomized into 3 treatment groups, receiving PRF stimulation of the SSN or physical therapy or both of them. After baseline examination, all patients will be given a full explanation of the treatment protocol and will be required to sign a written informed consent for study participation and for publication of the results. All the data collectors, surgeons, statistical analysts, as well as result assessors are not aware of grouping assignment. The outcomes include Constant score, visual analog scale score, range of motion, and strength.

Results:

This protocol will provide a reliable theoretical basis for the following research.

Conclusion:

It is assumed that there will be a remarkable difference in postoperative outcomes between the intervention and control groups.

Trial registration number:

10.17605/OSF.IO/PZ9ES.
Update in clinical management for gallbladder neuroendocrine carcinoma
Authors: Chu Hongwu , Shi Ying , Liu Junwei , Huang Dongsheng , Zhang Jungang , Dou Changwei
Published: April 2021

Background:

Gallbladder neuroendocrine carcinoma (GB-NEC) is rare and there are few reports at present. We sought to review the current knowledge of GB-NEC and provide recommendations for clinical management.

Methods:

A systemic literature research was conducted in the websites of Pubmed, Medline, Web of Science, CNKI, Wanfang Data using the keywords including gallbladder combined with neuroendocrine carcinoma or neuroendocrine tumor or neuroendocrine neoplasm. Two reviewers independently screened the articles by reading the title, abstract and full-text.

Results:

In computed tomography (CT) and magnetic resonance imaging (MRI) examination, a well-defined margin, gallbladder replacing type with larger hepatic and lymphatic metastases could be helpful for differential diagnosis of GB-NEC and gallbladder adenocarcinoma (GB-ADC). Older age, unmarried status, large tumor size (>5 cm), positive margins, and distant Surveillance, Epidemiology and End result (SEER) stage are independently associated with poor survival. Surgical resection remains as the preferred and primary treatment. The potential survival benefit of lymphadenectomy for patients remains controversial. Platinum-based postoperative adjuvant chemotherapy may improve the survival. The efficacy of other treatments including immunotherapy, targeted therapy and somatostatin analogue needs further investigation.

Conclusion:

Typical imaging features could be helpful for preoperative diagnosis. Age, margin status, tumor size, marital status, histopathologic subtype and SEER stage may be independent predictors for the survival. Remarkable advances regarding the treatment for GB-NEC have been achieved in recent years. Further studies are needed to investigate the survival benefit of lymphadenectomy for patients with GB-NEC.
Hyperparathyroidism presenting as hyperemesis and acute pancreatitis in pregnancy
Authors: Tsai Wen-Hsuan , Lee Chun-Chuan , Cheng Shih-Ping , Zeng Yi-Hong
Published: April 2021

Rationale:

Nausea and vomiting are common in the early period of pregnancy and rarely seen as an overture to pancreatitis.

Patient concerns:

Here, we describe a 31-year-old pregnant woman who presented with progressive nausea and vomiting followed by severe epigastric pain. Biochemical data and sonographic features confirmed the occurrence of acute pancreatitis. Accompanying electrolyte abnormalities included hypercalcemia and hypokalemia. Her condition stabilized following medical treatment, but hypercalcemia persisted despite intravenous fluids and furosemide administration.

Diagnoses:

A diagnosis of primary hyperparathyroidism was made based on the elevated parathyroid hormone level and urinary calcium-to-creatinine clearance ratio.

Interventions:

Localization study with neck ultrasonography indicated left inferior parathyroid adenoma. She underwent parathyroidectomy successfully and made an uneventful recovery.

Outcomes:

At 37 weeks of gestation, she had a serum calcium level of 8.8 mg/dL and normal parathyroid hormone of 28.55 pg/mL. A healthy baby weighing 3180 g was delivered smoothly with no clinical nor biochemical evidence of hypocalcemia.

Lessons:

Although primary hyperparathyroidism during pregnancy is usually asymptomatic, patients may present with atypical manifestations such as hyperemesis and pancreatitis. Proper diagnosis and timely intervention are crucial to minimizing potential hazards to both mother and fetus.
Impact of Enteral Nutrition Within 24 Hours Versus Between 24 and 48 Hours in Patients With Severe Acute Pancreatitis
Authors: Nakashima Ikue , Horibe Masayasu , Sanui Masamitsu , Sasaki Mitsuhito , Sawano Hirotaka , Goto Takashi , Ikeura Tsukasa , Takeda Tsuyoshi , Oda Takuya , Yasuda Hideto , Ogura Yuki , Miyazaki Dai , Kitamura Katsuya , Chiba Nobutaka , Ozaki Tetsu , Yamashita Takahiro , Koinuma Toshitaka , Oshima Taku , Yamamoto Tomonori , Hirota Morihisa , Moriya Takashi , Shirai Kunihiro , Izai Junko , Takeda Kazunori , Sekino Motohiro , Iwasaki Eisuke , Kanai Takanori , Mayumi Toshihiko
Published: April 2021

Objectives

In patients with severe acute pancreatitis (SAP), early enteral nutrition (EN) is recommended by major clinical practice guidelines, but the exact timing for the initiation of EN is unknown.

Methods

We conducted a post hoc analysis of the database for a multicenter (44 institutions) retrospective study of patients with SAP in Japan. The patients were classified into 3 groups according to the timing of EN initiation after the diagnosis of SAP: within 24 hours, between 24 and 48 hours, and more than 48 hours. The primary outcome was in-hospital mortality.

Results

Of the 1094 study patients, 176, 120, and 798 patients started EN within 24 hours, between 24 and 48 hours, and more than 48 hours after SAP diagnosis, respectively. On multivariable analysis, hospital mortality was significantly better with EN within 48 hours than with more than 48 hours (adjusted odds ratio, 0.49; 95% confidence interval, 0.29–0.83; P < 0.001) but did not significantly differ between the groups with EN starting within 24 hours and between 24 and 48 hours (P = 0.29).

Conclusions

Enteral nutrition within 24 hours may not confer any additional benefit on clinical outcomes compared with EN between 24 and 48 hours.
Case Report: Peripheral Retinal Ischemia and Retinal Neovascularization in von Willebrand Disease
Authors: Quan Steven C. , Skondra Dimitra
Published: April 2021

SIGNIFICANCE

Although von Willebrand disease is the most common inherited bleeding disorder, there are only a few published reports of ocular complications. To our knowledge, this is the first case of peripheral retinal ischemia and retinal neovascularization in a patient with von Willebrand disease.

PURPOSE

This study aimed to demonstrate the value of multispecialty care when exploring a diagnosis for bilateral retinopathy.

CASE REPORT

A 55-year-old African American woman presented with peripheral retinal hemorrhages on routine examination. She was asymptomatic and did not have any personal or family history of bleeding disorders. Blood work was ordered, and she was referred to a retinal specialist who found peripheral telangiectasia, retinal ischemia, and leakage on fluorescein angiography, consistent with retinal neovascularization. Laser photocoagulation was performed while numerous specialists were consulted to determine the cause for her retinopathy. Laboratory testing confirmed low-grade type 1 von Willebrand disease. She was monitored without systemic treatment. She remained stable and asymptomatic, but her retinal neovascularization did not regress fully, so laser treatment was repeated.

CONCLUSIONS

This case described a new finding of peripheral retinal ischemia and retinal neovascularization in von Willebrand disease. It was discovered in an asymptomatic patient who did not have a history of bleeding but presented with bilateral retinal hemorrhages. Diagnosis was challenging because of the high degree of variation in this bleeding disorder, requiring extensive testing and careful consideration of the individual's clinical profile. Most people with von Willebrand disease do not know they have the disease because symptoms are mild or absent, so most cases are unreported. The von Willebrand factor is poorly recognized in ocular disease, but given its role in angiogenesis, it may be a valuable target to consider in future research.
Low Vision and Dry Eye: Does One Diagnosis Overshadow the Other?
Authors: Bitton Etty , Arsenault Roxanne , Bourbonnière-Sirard Geneviève , Wittich Walter
Published: April 2021

SIGNIFICANCE

The prevalence of dry eye disease and low vision increases with age; they share risk factors and can be the result of underlying common causes. They are generally studied separately; however, combining these perspectives is relevant for research on assistive technology given that sustained focus affects the tear film because of decreased blinking rates.

PURPOSE

The objective of this study was to elucidate to which extent dry eye disease risk factors, signs, and symptoms are assessed in low vision patients who receive an eye examination as part of their vision rehabilitation services.

METHODS

Using a retrospective chart review, dry eye disease risk factors, signs, or symptoms were extracted from 201 randomly selected files that contained an eye examination in the past 5 years from two vision rehabilitation centers.

RESULTS

Demographic variables of charts from the two sites did not differ (mean visual acuity, 0.85 logMAR [standard deviation, 0.53; range, 0 to 2.3]; mean age, 71.2 years [standard deviation, 19 years; range, 24 to 101 years]). Fifty charts (25%) mentioned at least one dry eye disease symptom. Sixty-one charts (30.3%) reported systemic medications that can exacerbate dry eye disease, whereas 99 (49.2%) contained at least one systemic disease thought to contribute to dry eye disease symptoms; 145 (72.1%) mentioned at least one type of ocular surgery. Artificial tears were documented in 74 charts (36.8%). Few specific dry eye tests were performed, with the exception of corneal integrity assessment reported in 18 charts (8.95%).

CONCLUSIONS

Low vision patients have multiple risk factors for dry eye disease; however, dry eye disease tests were not frequently performed in comprehensive low vision eye examinations in this sample. More efforts should be made to assess dry eye disease to enhance comfort and functional vision, especially with the increasing demands of digital devices as visual aids.
A Novel Stimulus to Improve Perimetric Sampling within the Macula in Patients with Glaucoma
Authors: Alluwimi Muhammed S. , Swanson William H. , King Brett J.
Published: April 2021

SIGNIFICANCE

Identifying glaucomatous damage to the macula has become important for diagnosing and managing patients with glaucoma. In this study, we presented an approach that provides better perimetric sampling for the macular region, by testing four locations, with a good structure-function agreement.

PURPOSE

We previously presented a basis for customizing perimetric locations within the macula. In this study, we aimed to improve perimetric sampling within the macula by presenting a stimulus at four locations, with maintaining a good structure-function agreement.

METHODS

We tested one eye each of 30 patients (aged 50 to 88 years). Patients were selected based on observed structural damage to the macula, whereas perimetric defect (using 24-2) did not reflect the locations and extent of this damage. We used en face images to visualize retinal nerve fiber bundle defects. To measure perimetric sensitivities, we used a blob stimulus (standard deviation of 0.25°) at the 10-2 locations. A perimetric defect for a location was defined as any value equal to or deeper than −4, −5, and −6 dB below the mean sensitivity for 37 age-similar controls (aged 47 to 78 years). We also presented an elongated sinusoidal stimulus for 20 patients at four locations within the macula, in which we defined a perimetric defect as any value below the 2.5th percentile from controls.

RESULTS

The −4, −5, and −6 dB criteria identified perimetric defects in 14, 13, and 11 patients, respectively. When testing with the elongated stimulus, 18 patients were identified with perimetric defect. The perimetric defects were consistent with the structural damage.

CONCLUSIONS

The elongated stimulus showed a good structure-function agreement with only four testing locations as compared with 68 locations used with the blob stimulus. This demonstrates a clinical potential for this new stimulus in the next generation of perimetry.
The Impact of Incubation Conditions on In Vitro Phosphatidylcholine Deposition on Contact Lens Materials
Authors: Walther Hendrik , Lorentz Holly , Heynen Miriam , Kay Lise , Jones Lyndon W.
Published: April 2021

SIGNIFICANCE

Previous in vitro measurements of contact lenses commonly investigate the impact of nonpolar tear film lipids (i.e., sterols). Polar lipids, however, are equally important stabilizing components of the tear film. This research explores and presents further knowledge about various aspects of polar lipid uptake that may impact contact lens performance.

PURPOSE

This study evaluated the impact of incubation time, lipid concentration, and replenishment of an artificial tear solution (ATS) on the uptake of phosphatidylcholine (PC) onto conventional hydrogel (CH) and silicone hydrogel (SH) contact lens materials.

METHODS

Four SHs and two CH lens materials (n = 4) were soaked in a complex ATS containing radioactive 14C-PC as a probe molecule. Phosphatidylcholine uptake was monitored at various incubation time points (1, 3, 7, 14, and 28 days), with different ATS lipid concentrations (0.5×, 1×, 2×) and with and without regular replenishment of the ATS. Phosphatidylcholine was extracted from the lenses, processed, and counted by a β counter, and accumulated PC (μg/lens) was extrapolated from standard lipid calibration curves.

RESULTS

All materials exhibited increasing PC deposition over time. Conventional hydrogel materials showed significantly lower PC uptake rates (P < .001) than any of the SH materials. Increasing lipid concentration in the ATS resulted in increased PC binding onto the contact lens materials (P < .001). Replenishing the ATS every other day, however, impacted the PC deposition differently, showing increased binding (P < .001) on CHs and reduced PC deposition for SH materials (P < .001).

CONCLUSIONS

Length of incubation, lipid concentration in the ATS, and renewal of the incubation solution all influenced the amount of PC that sorbed onto various lens materials and therefore need to be considered when conducting future in vitro deposition studies.
CD34-negative Solitary Fibrous Tumor
Authors: Dermawan Josephine K. , Rubin Brian P. , Kilpatrick Scott E. , Gjorgova Gjeorgjievski Sandra , Fritchie Karen J. , Goldblum John R. , McKenney Jesse K. , Billings Steven D.
Published: April 2021

CD34-negative solitary fibrous tumors (SFTs) are rare and have not been comprehensively studied. We retrospectively reviewed all cases of SFT confirmed with STAT6 immunohistochemistry and/or STAT6 gene fusion between 2013 and 2020 and collected pertinent clinicopathologic parameters. Of a total of 244 cases, 25 (10%) lacked CD34 expression by immunohistochemistry. Compared with CD34-positive SFT, CD34-negative SFT are more likely to arise in the head and neck area (32% vs. 24%, P=0.02) and present as metastatic disease (28% vs. 1%, P<0.0001). A significantly higher percentage of CD34-negative SFT exhibit high-grade cytologic atypia (hypercellularity, round cell or anaplastic morphology, nuclear pleomorphism, etc.) (48% vs. 22%, P=0.0073). There are no significant differences in the distributions of age, sex, tumor size, mitotic count, tumor necrosis, or risk stratification between CD34-negative and CD34-positive SFT. In addition, only 56% of CD34-negative SFT display a typical hemangiopericytoma-like vascular pattern. Special histologic features among CD34-negative SFT include prominent alternating hypercellular or fibrous and hypocellular myxoid areas with curvilinear vessels mimicking low-grade fibromyxoid sarcoma, pulmonary edema-like microcystic changes, and prominent amianthoid collagen fibers. In conclusion, compared with their CD34-positive counterparts, CD34-negative SFT is more likely to present as metastatic disease, show high-grade nuclear atypia, and lack the characteristic hemangiopericytoma-like vasculature, posing a unique diagnostic challenge. The use of STAT6 immunohistochemistry and/or molecular studies may be prudent in soft tissue tumors that appear CD34 negative and lack conventional SFT histopathologic characteristics.
Quality and Safety in Healthcare, Part LXXXVII
Authors: Harolds Jay A.
Published: April 2021

The Framework for Safe, Reliable, and Effective Care (Framework) and the combined TeamSTEPPS and CUSP programs have many similarities to improve safety including the use of teams, excellent communication, safety culture, engaging patients, and leadership. However, the Framework has a focus on the Model for Improvement, and the TeamSTEPPS and CUSP programs emphasize other subjects including handoffs, the membership of teams, coaching, and spreading changes.
Thoracic Extradural Paraganglioma Localized on 68Ga-DOTANOC PET/CT
Authors: Sachani Hemant , Tripathi Madhavi , Madhusudan Kumble Seetharama , Semalti Kapil , Shanker Shiv , ArunRaj Sreedharan Thankarajan , Bal Chandrasekhar
Published: April 2021

We present the case of a 33-year-old woman with complaints of headache and palpitations with raised urinary catecholamines. Ultrasound of the abdomen was noncontributory, and the patient was referred for 68Ga-DOTANOC PET/CT, which revealed tracer accumulation in the thecal sac/spinal canal at D5–D7 level, suggestive of a thoracic paraganglioma. MRI of the spine subsequently confirmed the presence of an extradural mass in the spinal canal extending from D4 to D8.
Metanephric Adenoma Mimicking Renal Cell Carcinoma on 99mTc-MIBI SPECT/CT
Authors: Gong Jing , Dong Aisheng , Shao Chengwei
Published: April 2021

Metanephric adenoma is a rare benign renal tumor. A 49-year-old woman presented with a left renal pelvic mass detected by ultrasound. Enhanced CT of the kidney showed slight enhancement of the mass. For characterization of the mass, 99mTc-MIBI SPECT/CT was performed showing photopenia of the mass. Renal cell carcinoma was suspected. The mass was removed surgically. Metanephric adenoma was confirmed by histopathology. This case indicates that metanephric adenoma can appear cold on 99mTc-MIBI SPECT/CT, mimicking renal cell carcinoma.
Clostridioides difficile toxins enhanced the in vitro production of CXC chemokine ligand 2 and tumor necrosis factor-α via Toll-like receptors in macrophages
Authors: McKee Hiroe Konishi , Kajiwara Chiaki , Yamaguchi Tetsuo , Ishii Yoshikazu , Shimizu Norikazu , Ohara Akira , Tateda Kazuhiro
Published: April 2021

Introduction.Clostridioides difficileinfection (CDI) causes toxin-mediated enteropathy, such as antibiotic-associated diarrhoea and pseudomembranous colitis. Rho-glucosylating toxin A (TcdA) and toxin B (TcdB) have been clearly implicated in pathogenesis, whereas the virulence of binary toxin (CDT) is still debated.

Hypothesis statement.We hypothesized that CDT is involved in the host immune response and plays a pivotal role in establishing virulence by modulating pro-inflammatory cytokine production; this is achieved through the integral Toll-like receptor (TLR) signalling pathways.

Aim.The aim of the present study was to determine whether and how CDT impacts macrophages compared to TcdA or TcdB by examining the induction of CXC chemokine ligand 2 (CXCL2) and tumour necrosis factor-α (TNF-α), both of which are crucial in mediating local and systematic inflammatory responses.

Methodology.RAW264.7 cells or transfected human embryonic kidney (HEK) 293 T cells were incubated with TcdA, TcdB, or CDT. In some experiments, a neutralizing antibody against TLR2 or TLR4, or myeloid differentiation 88 inhibitory peptide were added. The amount of CXCL2 and TNF-α secreted was then measured.

Results.In RAW264.7 macrophages, CXCL2 and TNF-α were produced via the Toll-like receptor 2 (TLR2) or Toll-like receptor 4 (TLR4) pathway in a TcdA, TcdB, or CDT dose-dependent manner. Interleukin-8 secretion was induced in TLR4/MD2/CD14-transfected, but not in TLR2-transfected, HEK 293 T cells following TcdB or CDT exposure.

Conclusion.Our results showed thatC. difficiletoxins, including CDT, enhanced macrophage-mediated CXCL2 and TNF-α production via TLR2 and TLR4, indicating that CDT affects host immune responses.
Suboptimal response to COVID-19 mRNA vaccines in hematologic malignancies patients
Authors: Agha Mounzer , Blake Maggie , Chilleo Charles , Wells Alan , Haidar Ghady
Published: April 2021

Studies describing SARS-CoV-2 immune responses following mRNA vaccination in hematology malignancy (HM) patients are virtually non-existent. We measured SARS-CoV-2 IgG production in 67 HM patients who received 2 mRNA vaccine doses. We found that 46% of HM patients did not produce antibodies and were therefore vaccine non-responders. Patients with B-cell CLL were at a particularly high risk, as only 23% had detectable antibodies despite the fact that nearly 70% of these patients were not undergoing cancer therapy. HM patients should be counseled about the ongoing risk of COVID-19 despite vaccination. Routine measurement of post-vaccine antibodies in HM patients should be considered. Novel strategies are needed to prevent COVID-19 in these individuals.
Spatial expression programs of the intestinal follicle-associated epithelium
Authors: Cohen Noam , Massalha Hassan , Ben-Moshe Shani , Egozi Adi , Rozenberg Milena , Halpern Keren Bahar , Itzkovitz Shalev
Published: April 2021

The intestine is lined with isolated lymphoid follicles (ILFs) that facilitate sampling of luminal antigens to elicit immune responses. Technical challenges related to the scarcity and small sizes of ILFs and their follicle-associated epithelium (FAE) impeded the characterization of their spatial gene expression programs. Here, we combined RNA sequencing of laser capture microdissected tissues with single molecule transcript imaging to obtain a spatial gene expression map of the ILF and its associated FAE in the mouse small intestine. We identified zonated expression programs in both follicles and FAEs, with a decrease in enterocyte anti-microbial and absorption programs and a partial induction of expression programs normally observed at the villus tip. We further identified Lepr+ sub-epithelial telocytes at the FAE top, which are distinct from villus-tip Lgr5+ telocytes. Our analysis exposes the epithelial and mesenchymal cell states associated with ILFs.
LncRNA-UCA1 Alleviates Septic Acute Kidney Injury through Regulating Endoplasmic Reticulum Stress in LPS-treated HK-2 Cells
Authors: Yu TT , Cai FL , Niu J
Published: April 2021

Objective

Septic acute kidney injury (AKI) is an important cause of death in patients with sepsis. This study sought to explore the function of the long noncoding RNA, urothelial carcinoma associated 1 (lncRNA-UCA1), in septic AKI and determine the underlying molecular mechanism.

Methods

HK-2 cells were treated with lipopolysaccharide (LPS) to establish anin vitromodel of septic AKI. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of lncRNA-UCA1. CCK-8 assay was used to detect the viability of HK-2 cells. Western blotting was utilized to examine protein expression. The contents of SOD, GSH, MDA, and ROS were determined using commercial kits. The apoptosis rate was calculated using TUNEL staining and flow cytometry.

Results

LncRNA-UCA1 was down-regulated in LPS-treated HK-2 cells. LPS significantly reduced the content of SOD and GSH in HK-2 cells, increased the production of MDA and ROS, and led to an increase in the rate of apoptosis. However, overexpression of lncRNA-UCA1 protected HK-2 cells from oxidative stress and apoptosis. Furthermore, LPS induced endoplasmic reticulum (ER) stress in HK-2 cells, which was inhibited by overexpression of lncRNA-UCA1.

Conclusion

Overexpression of lncRNA-UCA1 inhibited LPS-induced oxidative stress and apoptosis of HK-2 cells by suppressing ER stress.
Hda1C restricts the transcription initiation frequency to limit divergent non-coding RNA transcription
Authors: Gowthaman Uthra , Ivanov Maxim , Schwarz Isabel , Patel Heta P. , Müller Niels A. , García-Pichardo Desiré , Lenstra Tineke L. , Marquardt Sebastian
Published: April 2021

Nucleosome-depleted regions (NDRs) at gene promoters support initiation of RNA Polymerase II transcription. Interestingly, transcription often initiates in both directions, resulting in an mRNA, and a divergent non-coding (DNC) transcript with an unclear purpose. Here, we characterized the genetic architecture and molecular mechanism of DNC transcription in budding yeast. We identified the Hda1 histone deacetylase complex (Hda1C) as a repressor of DNC in high-throughput reverse genetic screens based on quantitative single-cell fluorescence measurements. Nascent transcription profiling showed a genome-wide role of Hda1C in DNC repression. Live-cell imaging of transcription revealed that Hda1C reduced the frequency of DNC transcription. Hda1C contributed to decreased acetylation of histone H3 in DNC regions, supporting DNC repression by histone deacetylation. Our data support the interpretation that DNC results as a consequence of the NDR-based architecture of eukaryotic promoters, but that it is governed by locus-specific repression to maintain genome fidelity.
Genomic and phenotypic characterization of finger millet indicates a complex diversification history
Authors: Bančič Jon , Odeny Damaris A. , Ojulong Henry F. , Josiah Samuel M. , Buntjer Jaap , Gaynor R. Chris , Hoad Stephen P. , Gorjanc Gregor , Dawson Ian K.
Published: April 2021

Advances in sequencing technologies mean that insights into crop diversification aiding future breeding can now be explored in crops beyond major staples. For the first time, we use a genome assembly of finger millet, an allotetraploid orphan crop, to analyze DArTseq single nucleotide polymorphisms (SNPs) at the sub-genome level. A set of 8,778 SNPs and 13 agronomic traits characterizing a broad panel of 423 landrace accessions from Africa and Asia suggested the crop has undergone complex, context-specific diversification consistent with a long domestication history. Both Principal Component Analysis and Discriminant Analysis of Principal Components of SNPs indicated four groups of accessions that coincided with the principal geographic areas of finger millet cultivation. East Africa, the considered origin of the crop, appeared the least genetically diverse. A Principal Component Analysis of phenotypic data also indicated clear geographic differentiation, but different relationships among geographic areas than genomic data. Neighbour-joining trees of sub-genomes A and B showed different features which further supported the crop’s complex evolutionary history. Our genome-wide association study indicated only a small number of significant marker-trait associations. We applied then clustering to marker effects from a ridge regression model for each trait which revealed two clusters of different trait complexity, with days to flowering and threshing percentage among simple traits, and finger length and grain yield among more complex traits. Our study provides comprehensive new knowledge on the distribution of genomic and phenotypic variation in finger millet, supporting future breeding intra- and inter-regionally across its major cultivation range.

Core ideas

8,778 SNPs and 13 agronomic traits characterized a panel of 423 finger millet landraces.

4 clusters of accessions coincided with major geographic areas of finger millet cultivation.

A comparison of phenotypic and genomic data indicated a complex diversification history.

This was confirmed by the analysis of allotetraploid finger millet’s separate sub-genomes.

Comprehensive new knowledge for intra- and inter-regional breeding is provided.
The meta-gut: Hippo inputs lead to community coalescence of animal and environmental microbiomes
Authors: Dutton Christopher L. , Subalusky Amanda L. , Sanchez Alvaro , Estrela Sylvie , Lu Nanxi , Hamilton Stephen K. , Njoroge Laban , Rosi Emma J. , Post David M.
Published: April 2021

All animals carry specialized microbiomes, and their gut microbiotas in particular are continuously released into the environment through excretion of waste. Here we propose themeta-gutas a novel conceptual framework that addresses the ability of the gut microbiome released from an animal to function outside the host and potentially alter ecosystem processes mediated by microbes. An example considered here is the hippopotamus (hippo) and the pools they inhabit. Hippo pool biogeochemistry and fecal and pool water microbial communities were examined through field sampling and an experiment. Sequencing using 16S RNA methods revealed that the active microbial communities in hippo pools that received high inputs of hippo feces are more similar to the hippo gut microbiome than other nearby aquatic environments. The overlap between the microbiomes of the hippo gut and the waters into which they excrete therefore constitutes ameta-gutsystem with potentially strong influence on the biogeochemistry of pools and downstream waters. We propose that themeta-gutmay be present where other species congregate in high densities, particularly in aquatic environments.

Significance

Animals can have considerable impacts on biogeochemical cycles and ecosystem attributes through the consumption of resources and physical modifications of the environment. Likewise, microbial communities are well known to regulate biogeochemical cycles. This study links those two observations by showing that the gut microbiome in waste excreted by hippos can persistex-situin the environment and potentially alter biogeochemical cycles. This “meta-gut” system may be present in other ecosystems where animals congregate, and may have been more widespread in the past before many large animal populations were reduced in range and abundance.
Non-invasive real-time access to the output of the spinal cord via a wrist wearable interface
Authors: Mendez Irene , Barsakcioglu Deren Y. , Vujaklija Ivan , Wetmore Daniel Z. , Farina Dario
Published: April 2021

Despite the promising features of neural interfaces, their trade-off between information transfer and invasiveness has limited translation and viability outside research settings. Here, we present a non-invasive neural interface that provides access to spinal motoneuron activities from a sensor band at the wrist. The interface decodes electric signals present at the tendon endings of the forearm muscles by using a model of signal generation and deconvolution. First, we evaluated the reliability of the interface to detect motoneuron firings, and thereafter we used the decoded neural activity for the prediction of finger movements in offline and real-time conditions. The results showed that motoneuron activity decoded from the wrist accurately predicted individual and combined finger commands and therefore allowed for highly accurate real-time control. These findings demonstrate the feasibility of a wearable, non-invasive, neural interface at the wrist for precise real-time control based on the output of the spinal cord.
Prior Pro-inflammatory Polarization Changes the Macrophage Response to IL-4
Authors: O’Brien Erin M. , Spiller Kara L.
Published: April 2021

Tissue repair is largely regulated by diverse macrophage populations whose functions are timing- and context-dependent. The early phase of healing is dominated by pro-inflammatory macrophages, also known as M1, followed by the emergence of a distinct and diverse population that is collectively referred to as M2. The extent of the diversity of the M2 population is unknown. M2 macrophages may originate directly from circulating monocytes or from phenotypic switching of pre-existing M1 macrophages within the site of injury. The differences between these groups have not been investigated, but have major implications for understanding and treating pathologies characterized by deficient M2 activation, such as chronic wounds, which also exhibit diminished M1 macrophage behavior. This study investigated the influence of prior M1 activation on human macrophage polarization to an M2 phenotype in response to IL-4 treatment in vitro. Compared to unactivated (M0) macrophages, M1 macrophages upregulated several receptors that promote the M2 phenotype, including the primary receptor for IL-4. M1 activation also changed the macrophage response to treatment with IL-4, generating an M2-like phenotype with a distinct gene and protein expression signature compared to M2 macrophages prepared directly from M0 macrophages. Functionally, compared to M0-derived M2 macrophages, M1-derived M2 macrophages demonstrated increased migratory response to SDF-1α, and conditioned media from these macrophages promoted increased recruitment of endothelial cells in transwell assays. Together, these findings indicate the importance of prior M1 activation in regulating subsequent M2 behavior, and suggest that augmentation of M1 behavior may be a therapeutic target in dysfunctional tissue repair.

Summary sentence

M1 macrophages that are switched to an M2 phenotype exhibit a distinct functional phenotype compared to M2 macrophages derived directly from unactivated (M0) macrophages.
Pre-Stimulus Alpha-Band Phase Gates Afferent Visual Cortex Responses
Authors: Dou Wei , Morrow Audrey , Iemi Luca , Samaha Jason
Published: April 2021

The neurogenesis of alpha-band (8-13 Hz) activity has been characterized across many different animal experiments. However, the functional role that alpha oscillations play in perception and behavior has largely been attributed to two contrasting hypotheses, with human evidence in favor of either (or both or neither) remaining sparse. On the one hand, alpha generators have been observed in relay sectors of the visual thalamus and are postulated to phasically inhibit afferent visual input in a feedforward manner1–4. On the other hand, evidence also suggests that the direction of influence of alpha activity propagates backwards along the visual hierarchy, reflecting a feedback influence upon the visual cortex5–9. The primary source of human evidence regarding the role of alpha phase in visual processing has been on perceptual reports10–16, which could be modulated either by feedforward or feedback alpha activity. Thus, although these two hypotheses are not mutually exclusive, human evidence clearly supporting either one is lacking. Here, we present human subjects with large, high-contrast visual stimuli that elicit robust C1 event-related potentials (ERP), which peak between 70-80 milliseconds post-stimulus and are thought to reflect afferent primary visual cortex (V1) input17–20. We find that the phase of ongoing alpha oscillations modulates the global field power (GFP) of the EEG during this first volley of stimulus processing (the C1 time-window). On the standard assumption21–23that this early activity reflects postsynaptic potentials being relayed to visual cortex from the thalamus, our results suggest that alpha phase gates visual responses during the first feed-forward sweep of processing.
The determinants of subjective sleep depth: insights from a high-density-EEG study with serial awakenings
Authors: Stephan Aurélie , Lecci Sandro , Cataldi Jacinthe , Siclari Francesca
Published: April 2021

What accounts for the feeling of being deeply asleep? Standard sleep recordings only incompletely reflect subjective aspects of sleep and some individuals with so-called sleep misperception frequently feel awake although sleep recordings indicate clear-cut sleep. To identify the determinants of the subjective perception of sleep, we performed 787 awakenings in 20 good sleepers and 10 individuals with sleep misperception and interviewed them about their subjective sleep depth while they underwent high-density EEG sleep recordings. Surprisingly, in good sleepers, sleep was subjectively lightest in the first two hours of Non-rapid eye movement (NREM) sleep, generally considered the ‘deepest’ sleep, and deepest in rapid eye movement (REM) sleep. Compared to good sleepers, sleep misperceptors felt more frequently awake during sleep and reported lighter REM sleep. At the EEG level, spatially widespread high-frequency power was inversely related to subjective sleep depth in NREM sleep in both groups and in REM sleep in misperceptors. Subjective sleep depth positively correlated with dream-like qualities of reports of mental activity. These findings challenge the widely held notion that slow wave sleep best accounts for feeling deeply asleep. Instead, they indicate that subjective sleep depth is inversely related to a neurophysiological process that predominates in early NREM sleep, becomes quiescent in REM sleep and is reflected in high-frequency EEG-activity. In sleep misperceptors, this process is more frequently active, more spatially widespread, and abnormally persists into REM sleep. These findings help identify the neuromodulatory systems involved in subjective sleep depth and are relevant for studies aiming to improve subjective sleep quality.