bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Risk of Angiotensin II Receptor Blocker Valsartan: A Population-based Study
Authors: Chan Tak Hon , Tsoi Man Fung , Yung Cheung Bernard Man
Published: January 2022

Nitrosamine contamination of generic valsartan was found in 2018. This study aimed to investigate whether long-term use of valsartan increases cancer risk. Patients prescribed valsartan or amlodipine (control group) from 1 January 1, 2003, to June 30, 2010, were identified using the Clinical Data Analysis and Reporting System of the Hong Kong Hospital Authority, a territory-wide database in Hong Kong. Patients previously diagnosed with cancer, prescribed both medications, taking the medication, or followed up for <1 year were excluded. Cancer incidence, adjusted for age, sex, and Charlson Comorbidity Index, was the primary outcome and was estimated using Poisson regression in R version 3.6.1. Among 5023 valsartan users and 3692 amlodipine users, 887 and 740 were diagnosed with cancers during median follow-up periods of 10.97 and 12.12 years, respectively. The adjusted incidence of cancer in valsartan and amlodipine users was 165.29 (95% confidence interval 154.76–175.53) and 180.12 (167.35–193.67) per 10,000 person-years, respectively. The cancer incidence rate ratio of valsartan relative to amlodipine was 0.94 (0.88–1.01). Adjusted incidence rate ratios of valsartan relative to amlodipine were significant for breast cancer (0.63, 0.46–0.86) only. Our findings do not suggest an increase in incidence of cancer with long-term valsartan use. The duration of follow-up of more than 10 years of the study provides the reassurance that an increase in cancer risk is unlikely. Further studies are needed to elucidate the long-term effect of valsartan use on the risk of specific types of cancer.
Repair of Breast Defect by Transfer of a Contralateral Internal Mammary Artery Perforator Flap
Authors: Yang Qingfeng , Wu Zankai , Zhang Xue , Feng Juan , Zhao Hengqiang , Liao Lingxia , Cui Le , Gong Yiping
Published: January 2022

This is a case report of a patient with a borderline phyllodes tumor in the left breast. Seventeen months after the resection of the phyllodes tumor from the patient’s left breast, the tumor occurred again 5 months ago in the surgical region. A large defect was generated after the extended resection of the left breast mass, and it was repaired with a contralateral internal mammary artery perforator flap. After the operation, bilateral breast symmetry was good, and the patient was satisfied with the shape of the breast. Postoperative follow-up was performed for 15 months, and no local recurrence was observed.
The risk of insomnia after surgical operation: A longitudinal, population-based, case-crossover study
Authors: Lin Wei-Chen , Chang Wen-Han , Bai Ya-Mei , Li Cheng-Ta , Chen Mu-Hong , Su Tung-Ping
Published: January 2022

Background:

The acute onset of insomnia following surgical operations has long been neglected, and long-term outcomes are not clear. Our aims were (1) to evaluate the risk of postoperative insomnia, (2) to identify which surgeries are related, and (3) to follow patients with postoperative insomnia for the development of major mental and physical disorders.

Methods:

We conducted a case-crossover study comprising 9898 participants with new-onset insomnia from the Taiwan National Health Insurance Research Database between 1997 and 2011. We determined the odds of having surgery in the case period (30 days) before the onset of insomnia by logistic regression analysis. Types of surgery that postoperative insomniacs had undergone were compared with age-/gender-/timing-matched controls. Longitudinal follow-up of postoperative and non-postoperative insomniacs was performed.

Results:

The odds ratio of surgical exposure vs. nonexposure within 30 days was 12.05 (p < 0.001) before new-onset insomnia. Surgery of musculoskeletal and nervous systems predisposed to insomnia. The duration of hypnotic drug use (0.83 years) was shorter and with a nearly 2-fold faster remission rate in postoperative than in non-postoperative insomniacs (1.45 years). Approximately 25% of each insomnia group developed persistent sleep disturbance.

Conclusion:

Surgery is associated with subsequent insomnia, which has a shorter duration and a faster remission than non-postoperative insomnia. Our data provide a reference for postoperative care, and warrant future studies.
mHealth Intervention to Improve Cardiometabolic Health in Rural Hispanic Adults
Authors: Rowland Sheri A. , Ramos Athena K. , Trinidad Natalia , Quintero Sophia , Johnson-Beller Rebecca , Struwe Leeza , Pozehl Bunny
Published: January 2022

Background

Hispanic/Latino adults have high rates of hypertension, obesity, and type II diabetes. Mobile health technologies (mHealth) are effective in supporting self-management of lifestyle behaviors; however, the effectiveness in rural Hispanic/Latino adults is unclear.

Objective

A pilot 12-week self-management mHealth intervention in rural Hispanic/Latino adults with cardiometabolic risk was conducted.

Methods

A randomized, 2-group (intervention and enhanced usual care) design was used to test the use of the MyFitnessPal app, a smart scale, and text messages to support daily self-monitoring of weight, food intake, and steps.

Results

Seventy participants enrolled. The intervention group had greater improvement in body mass index (P = .052) and waist circumference (P = .043) at 12 weeks and a trend toward greater fitness at 12 and 24 weeks. Both groups improved hemoglobin A1c level at 12 and 24 weeks.

Conclusions

mHealth using MyFitnessPal, smart scale, and text messages may be effective for improving aspects of cardiometabolic health in rural Hispanic/Latino adults.
Does Vestibulo-Ocular Reflex (VOR) Gain Correlate With Radiological Findings in the Semi-Circular Canals in Patients Carrying the p.Pro51Ser (P51S) COCH Variant Causing DFNA9? Relationship Between the Three-Dimensional Video Head Impulse Test (vHIT) and MR/CT Imaging
Authors: Salah Mahadi , Moyaert Julie , Vanderveken Olivier , Schepers Steven , Termote Bruno , Van Rompaey Vincent , Janssens de Varebeke Sebastien
Published: January 2022

Objective:

The primary aim was to determine whether 3D video-head-impulse-test vestibulo-ocular reflex (vHIT VOR)-gains correlate with computed tomography (CT) and magnetic resonance (MR) lesions in a series of carriers of the p.(Pro51Ser)-variant (P51S) in the COCH-gene (DFNA9). Secondary aim was to compare routine imaging with second peer review radiologic lecture.

Study Design:

Analytical cross-sectional study.

Setting:

Secondary referral center.

Patients:

Twenty-four p.P51S carriers with MR and CT images. Eighteen carriers were selected of whom both 3D-vHIT and imaging data were available within a time interval of 24 months.

Interventions:

All imaging data were reassessed by two independent neuroradiologists. vHIT VOR-gains were correlated with semi-circular canal (SCC) lesions.

Main Outcome Measures:

Correlation between vHIT VOR-gains and SCC lesions, and additional lesions detected during scientific lecture of imaging data.

Results:

The average gain of the ipsilateral labyrinth was significantly lower when positive CT (0.3215; p = 0.0122) and MR results (0.3215; p = 0.0134).

92% of ears presented MR lesions on at least one SCC, whereas this was 75% on CT. The posterior SCC is the most frequently affected on MR and CT. Second lecture led to nine additional MR and 16 CT lesions.

Conclusions:

Significant correlation was observed between radiological lesions at any SCC and lower average gain of the three ipsilateral SCC. The substantially larger number of lesions during scientific assessment stresses the need to fully inform radiologists concerning differential diagnosis to facilitate accurate diagnosis when planning imaging. Focal sclerosis and narrowing of SCC in DFNA9 represent a possible biomarker of advanced stages of otovestibular deterioration.
Reduction of Somatic Tinnitus Severity is Mediated by Improvement of Temporomandibular Disorders
Authors: van der Wal Annemarie , Michiels Sarah , Van de Heyning Paul , Gilles Annick , Jacquemin Laure , Van Rompaey Vincent , Braem Marc , Visscher Corine Mirjam , Topsakal Vedat , Truijen Steven , De Hertogh Willem
Published: January 2022

Background:

Successful orofacial treatment can reduce tinnitus severity in patients with somatic tinnitus (ST). However, it is still unclear to what extent the degree of reduction in temporomandibular disorders (TMD) actually contributes to the decrease in tinnitus severity after orofacial treatment. Therefore, the aim of this study was to analyze the mediating effect of reduction in TMD pain on the improvement of tinnitus severity after multidisciplinary orofacial treatment.

Methods:

A total of 80 patients with moderate to severe ST attributed to the temporomandibular region, were recruited from a tertiary tinnitus clinic. At baseline, patients were randomly assigned to the orofacial treatment group or to the control group. Both groups received a minimum of information and advice regarding their tinnitus complaints. The orofacial treatment group received orofacial physical therapy complemented with occlusal splints when needed, while the control group received no other treatment. A mediation analysis was performed according to the steps described by Baron and Kenny and the proportion of the mediating effect was calculated for the potential mediator: “change in TMD pain,” measured by a one-point decrease in TMD pain screener score.

Results:

Our analysis showed that 35% of the observed decrease in tinnitus severity can be attributed to a reduction in TMD pain. A significant total effect of orofacial treatment compared with control on the change in tinnitus functional index (TFI) score was found (B = 0.253 p = 0.025 Cl for B = 1.265–18.576). Orofacial treatment was also significantly related to the change in TMD pain (Exp (B) = 2.800, p = 0.034 Cl for Exp B 1.081–7.251). Additionally, the change in TMD pain screener score was significantly related to the change in TFI score (B = –0.273 p = 0.016 Cl for B = –19.875 to –2.119).

Conclusion:

Reduction of TMD pain is a mediating factor in the decrease of tinnitus severity after multidisciplinary orofacial treatment.

Practical Implications:

Orofacial treatment can be used to decrease tinnitus severity in patients with TMD related somatic tinnitus.
Cardiopulmonary Resuscitation Induced Posterior Rib Fractures in Nontraumatic Pediatric Deaths
Authors: Love Jennifer C. , Austin Dana , Giese Kristinza W. , Roe Susan J.
Published: January 2022

Posterior rib fractures are considered suspicious for nonaccidental injury when observed in infants without significant trauma history or underlying bone disease. The biomechanical mechanism postulated for causing posterior rib fractures is anterior/posterior compression of the chest with posterior levering of the rib head over the transverse process of the vertebra creating a focal area of stress. The recommended “2-thumb” cardiopulmonary resuscitation method involves the administrator placing both thumbs on the sternum of the patient, encircling the chest with the hands, and placing the finger tips lateral to the spine. From this position, the administrator compresses the chest in an anterior/posterior direction by pressing on the sternum. Theoretically, the 2-thumb method should focus all force on the sternum while the back is supported by the fingers limiting posterior levering of the ribs and reducing the risk of posterior rib fractures. However, posterior rib fractures have been found during the autopsy of infants who received 2-thumb cardiopulmonary resuscitation, had no traumatic history, had a nontraumatic cause of death, and had no indication of underlying bone disease. This case study series presents the demographics, birth histories, circumstances surrounding death, and autopsy findings of four such medical examiner cases.
Critical Care Unit Organizational and Personnel Factors Impact Cardiac Arrest Prevention and Rescue in the Pediatric Cardiac Population
Authors: Lasa Javier J. , Banerjee Mousumi , Zhang Wenying , Bailly David K. , Sasaki Jun , Bertrandt Rebecca , Raymond Tia T. , Olive Mary K. , Smith Andrew , Alten Jeffrey , Gaies Michael
Published: January 2022

OBJECTIVES:

Patient-level factors related to cardiac arrest in the pediatric cardiac population are well understood but may be unmodifiable. The impact of cardiac ICU organizational and personnel factors on cardiac arrest rates and outcomes remains unknown. We sought to better understand the association between these potentially modifiable organizational and personnel factors on cardiac arrest prevention and rescue.

DESIGN:

Retrospective analysis of the Pediatric Cardiac Critical Care Consortium registry.

SETTING:

Pediatric cardiac ICUs.

PATIENTS:

All cardiac ICU admissions were evaluated for cardiac arrest and survival outcomes.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Successful prevention was defined as the proportion of admissions with no cardiac arrest (inverse of cardiac arrest incidence). Rescue was the proportion of patients surviving to cardiac ICU discharge after cardiac arrest. Cardiac ICU organizational and personnel factors were captured via site questionnaires. The associations between organizational and personnel factors and prevention/rescue were analyzed using Fine-Gray and multinomial regression, respectively, accounting for clustering within hospitals. We analyzed 54,521 cardiac ICU admissions (29 hospitals) with 1,398 cardiac arrest events (2.5%) between August 1, 2014, and March 5, 2019. For both surgical and medical admissions, lower average daily cardiac ICU occupancy was associated with better cardiac arrest prevention. Better rescue for medical admissions was observed for higher registered nursing hours per patient day and lower proportions of “part time” cardiac ICU physician staff (< 6 service weeks/yr). Increased registered nurse experience was associated with better rescue for surgical admissions. Increased proportion of critical care certified nurses, full-time intensivists with critical care fellowship training, dedicated respiratory therapists, quality/safety resources, and annual cardiac ICU admission volume were not associated with improved prevention or rescue.

CONCLUSIONS:

Our multi-institutional analysis identified cardiac ICU bed occupancy, registered nurse experience, and physician staffing as potentially important factors associated with cardiac arrest prevention and rescue. Recognizing the limitations of measuring these variables cross-sectionally, additional studies are needed to further investigate these organizational and personnel factors, their interrelationships, and how hospitals can modify structure to improve cardiac arrest outcomes.
It's a Hard Knock Life
Authors: Krishnan Kavita , Su Alice , Sigman Garry , Joyce Cara , Rech Megan A. , Long Christina M.
Published: January 2022

Objectives

The diagnosis and treatment of mild traumatic brain injuries (mTBIs) by emergency medicine providers is greatly varied. Because of the frequency and long-term consequences associated with pediatric head injuries, it is crucial that adequate counseling is provided in acute care settings. The purpose of our study is to evaluate existing practices at Loyola University Medical Center emergency department to address inconsistencies in diagnostic or discharge practices and determine future quality improvement measures.

Methods

A retrospective cohort study was conducted at an academic hospital emergency department of patient records from 2017 to 2020. Demographic, diagnostic, and discharge data were summarized, and Pearson χ2 tests and Fisher exact tests were performed to determine associations among patient characteristics and provider practices.

Results

A total of 1160 patients met inclusion criteria for analysis. In terms of diagnostic procedure, 31.6% of providers did not uniformly use existing screening criteria, such as PECARN, to determine if CT scans were needed for mTBI evaluation. Most discharge instructions were based on a generalized template on epic (91.9%). Only a minority of providers prepared patient-specific instructions through written, verbal, or other supplemental materials. The most common formats included epic only (46.1%), epic and personalized written instructions (20.2%), and epic and verbal instructions (12.4%). Follow-up care instructions were provided to 93% of patients who received discharged instructions, mainly for primary care (96.7%), sports medicine (1.58%), neurology (0.65%), or other providers (1.11%).

Conclusions

There is a lack of consistency in the evaluation and education of mTBI in pediatric patients. There is a need for personalized discharge instructions to ensure adequate patient and parent understanding and compliance. Further studies looking at long-term outcomes in these patients would also be beneficial.
Do Knee-Straining Activities Influence the Subchondral Bone Microarchitecture and Accelerate Knee Osteoarthritis Progression?
Authors: Li Mingyang , Zeng Yi , Nie Yong , Wu Yuangang , Liu Yuan , Wu Limin , Shen Bin
Published: January 2022

Background

Knee overload was detrimental to knee osteoarthritis subjects. We aim to analyze the association between the subchondral bone microarchitecture sclerosis and typical knee-straining activities.

Methods

The frequency of experiencing squatting, kneeling, lifting, and climbing of 481 knee osteoarthritis subjects was investigated. Subchondral bone microarchitecture (bone volume fraction, trabecular thickness, trabecular separation, and trabecular number) was measured by the fast imaging with steady-state free precession magnetic resonance imaging applying trabecular sequencing, at baseline and 12-mo follow-up. Logistic regression was conducted to investigate the relationship between microarchitecture change and each knee-straining activity, adjusted by age, sex, weight, and Kellgren-Lawrence grade. All data were from the Osteoarthritis Initiative.

Results

Long kneeling was associated with increased bone volume fraction (adjusted odds ratio = 1.16, confidence interval = 1.01–1.33) and trabecular number (adjusted odds ratio = 1.16, confidence interval = 1.02–1.33). Long squatting was associated with a lower risk of increased trabecular separation (adjusted odds ratio = 0.84, confidence interval = 0.71–0.98) and a higher risk of increased trabecular thickness (adjusted odds ratio = 1.29, confidence interval = 1.06–1.55). Long squatting also increased the medial compartment joint width narrowing (−0.21 in squatting group vs −0.03 in no squatting group, P < 0.05).

Conclusions

Knee osteoarthritis patients should avoid long squatting and kneeling, and subchondral bone microarchitecture possesses excellent potential as a monitoring indicator in subjects who kneel or squat for long.
Does Anesthetic Relief Correspond to Future Pain Relief?
Authors: Cushman Daniel M. , Knox Jordan , Kobayashi Jacqueline K. , Zarate Marisol , Wheelwright John C. , Monson Nicholas , English Joy , Teramoto Masaru
Published: January 2022

Objectives

The aim of the study was to prospectively evaluate the association between immediate pain relief from injections of local anesthetic with corticosteroid and subsequent pain relief up to 3 mos. The secondary aim was to examine the time until subjective pain relief after these injections.

Design

This was a single-center, prospective study of patients undergoing ultrasound-guided corticosteroid injections for musculoskeletal pain. Subjects completed follow-up surveys at 2 wks, 1 mo, and 3 mos postinjections. χ2 tests and sensitivity analysis were used to examine the primary outcome, at least 50% relief from the injection. Regression modeling examined the effects of demographic and injection-related variables on outcome measures.

Results

A total of 132 patients were enrolled (55% female, mean age 52 yrs). Response rates were 87.1% at 2 wks and 77.2% at 3 mos. The positive likelihood ratios from 50% initial pain relief ranged from 1.22 to 1.29 at the three time points, whereas the negative likelihood ratios ranged from 0.54 to 0.63. More than 75% of participants reported subjective pain relief by day 4 after injection.

Conclusions

The predictive value of immediate pain relief for subsequent longer-term pain relief from corticosteroid-anesthetic injections is not particularly high. Most patients will obtain pain relief within 4 days of a corticosteroid injection.
Simplified prosthetic rehabilitation of a patient with partial finger amputation after a firearm injury
Authors: Penitente Paulo Augusto , da Silva Emily Vivianne Freitas , Tabata Lucas Fernando , Goiato Marcelo Coelho , de Medeiros Rodrigo Antonio
Published: January 2022

Objective:

This study reports a clinical case of rehabilitation of a patient who had her left little finger amputated at the mesial phalanx because of a gunshot wound. The finger prosthesis was custom- made using a silicone.

Case description:

This study presents a clinical case of a female patient who had her left little finger amputated at the mesial phalanx because of a gunshot wound in 2016. The patient was attended at a reference center in maxillofacial rehabilitation in the city of Brasilia, Distrito Federal, Brazil, for the manufacture of a finger prosthesis. After molding, a finger waxing was obtained using the right little finger as a template. The waxing was later adjusted on the plaster model of the affected stump. The prosthesis was manufactured with silicone and intrinsically stained with a makeup powder. A water-based adhesive and a ring were used to generate a slight compression so that the prosthesis was retained on the stump.

Outcomes:

The rehabilitation showed satisfactory levels of stability, retention, and aesthetics, and it was usable and clinically acceptable, as observed in a follow-up appointment in February 2020.

Conclusions:

The complete or partial reestablishment of functions performed by important structures, such as the fingers, is essential to increase the quality of life of individuals, improving their performance of daily activities. In addition, reporting on this public health problem allows scientific advancement in the area.
Negative 68Ga–Prostate-Specific Membrane Antigen PET/CT Scan on a Recurrent Juvenile Nasopharyngeal Angiofibroma
Authors: Chandran Aswin , Verma Hitesh , Bhalla Ashu Seith , Kumar Rakesh , Kakkar Aanchal
Published: January 2022

We present the case of a left-sided recurrent juvenile nasopharyngeal angiofibroma (JNA) in a 16-year-old boy who underwent endoscopic excision 2 years back. The preoperative contrast-enhanced MRI and histopathology were in favor of JNA. The follow-up 68Ga–prostate-specific membrane antigen (PSMA) PET/CT scan at 3-month interval revealed complete clearance of disease. Currently, the patient presented with recurrent bleeding and nasal endoscopic examination, and contrast-enhanced MRI revealed a presence of a recurrent tumor. The tumor did not show any uptake on 68Ga-PSMA PET/CT, and postoperative histopathology evaluation confirmed the presence of JNA. Although regarded as a criterion-standard imaging modality for assessment of recurrent or residual JNA, 68Ga-PSMA PET/CT is never 100% specific.
Pheochromocytomatosis Treated With Peptide Receptor Radionuclide Therapy
Authors: Auerbach Martin S. , Livhits Masha J. , Yu Run
Published: January 2022

Pheochromocytomatosis refers to pheochromocytoma tumorlets developed as a result of seeding of tumor cells around the surgical bed due to intraoperative tumor capsule rupture and tumor cell spillage. As pheochromocytomatosis is relatively rare, optimal management is not clear. We describe a 42-year-old man with progressive pheochromocytomatosis despite surgical debulking. He did not have a family history of pheochromocytoma or harbor mutations in pheochromocytoma-predisposing genes. The pheochromocytomatosis tumorlets exhibited uptake on DOTATATE PET. He underwent PRRT (peptide receptor radionuclide therapy), which stabilized the pheochromocytomatosis progression. This case highlights the rare phenomenon of pheochromocytomatosis and the utility of PRRT in treating it.
Complementary Utility of Dopamine Transporter and Tau PET Imaging in the Diagnosis of Progressive Supranuclear Palsy
Authors: Jia Chenhao , Wu Meiqi , Yen Tzu-Chen , Li Yanfeng , Cui Ruixue
Published: January 2022

A 50-year-old woman developed gait disturbances, tendency to fall backwards, bradykinesia, and memory loss over the previous 6 months. Brain 18F-FDG PET/CT was unable to distinguish among APSs (atypical parkinsonian syndromes); PET investigations of dopamine transporter (DAT) function (11C-CFT) and tau pathology (18F-APN-1607) were performed. 11C-CFT PET revealed severe loss of striatal DAT function, whereas significant tau accumulation was observed in the brainstem, basal ganglia, and globus pallidus on 18F-APN-1607 PET. Such finding suggested diagnosis of PSP (progressive supranuclear palsy). This case highlights the value of DAT and tau PET imaging in diagnosis of PSP and differential diagnosis ofAPSs.
FDG PET/CT of Primary Breast Lymphoma in a Man
Authors: Ran Pengcheng , Li Hui , Hu Yongzhen , Chen Miao , Dong Aisheng
Published: January 2022

Primary lymphoma of the male breast is extremely rare. We describe FDG PET/CT findings in a man with primary breast lymphoma in his right breast. The breast tumor showed intense FDG uptake mimicking breast carcinoma.
Incidental Finding of Testicular Seminoma by 18F-Choline PET/CT in a Prostate Cancer Patient
Authors: Calabrò Anna , Bosio Giovanni , Drera Emma , Giubbini Raffaele , Bertagna Francesco
Published: January 2022

An 80-year-old man with a history of prostate cancer, treated with radical prostatectomy and bilateral obturator nodal dissection, underwent an 18F-choline PET/CT because of biochemical recurrence. The scan revealed an intense focal uptake in the right testicle. A subsequent orchifunicumlectomy demonstrated the presence of a classic seminoma. At present, 18F-FDG PET/CT is useful for initial staging of testicular cancer and determining the viability of residual masses >3 cm after completion of treatment, especially in patients with seminoma.
Tubercular Spondylitis
Authors: Bohil Amit , Seshadri Nagabhushan , Rathi Nitika , Fernando Rashika , Vinjamuri Sobhan
Published: January 2022

BCGosis is a rare complication of intravesical BCG immunotherapy as adjuvant therapy for urinary bladder cancer manifesting in the form of disseminated tuberculosis or organ-specific tuberculosis, rarely involving the vertebra. PSMA is overexpressed in prostate cancer but also expressed in a variety of benign and malignant conditions. We present a patient with incidental detection of abnormal uptake in a vertebral lesion during assessment of prostate cancer with 18F-PSMA PET/CT, subsequently proven to be vertebral osteitis, likely due to BCG immunotherapy. The case highlights the role of interdisciplinary patient assessment to confirm nature of abnormal foci on 18F-PSMA PET/CT.
Bone Tuberculous Granulomatous Inflammation Mimicking Malignancy on 68Ga-FAPI PET/CT
Authors: Gong Weidong , Yang Xiao , Mou Chunru , Liu Huipan , Zhang Chunyin
Published: January 2022

A 50-year-old woman presented with back pain for 1 month. Chest CT showed osteolytic destruction of T6 vertebral body. A malignancy was suspected. The patient was subsequently enrolled in the clinical trial of 68Ga-FAPI PET/CT. 68Ga-FAPI PET/CT revealed multiple bone destruction with increased FAPI activity. It was also highly suggestive of malignancy or metastases. However, pathological examination after T6 vertebral surgery confirmed the diagnosis of tuberculous granulomatous inflammation.
Relationship Between Endoscopic and Clinical Disease Activity With Fatigue in Inflammatory Bowel Disease
Authors: Kamp Kendra J. , Clark-Snustad Kindra , Barahimi Mitra , Lee Scott
Published: January 2022

Fatigue is a prevalent symptom among individuals with inflammatory bowel disease. Yet, few studies have examined the relationship between fatigue and endoscopic disease activity. A retrospective chart review was conducted to determine the prevalence of fatigue based on endoscopic inflammation and clinical disease activity and describe the factors associated with fatigue among adults with inflammatory bowel disease. One hundred sixty patients were included. The majority had Crohn disease (72.5%), with an average age of 40.5 years. Sixty-one percent reported fatigue. Both endoscopic (p = .03) and clinical disease activities (p = .001) were significantly associated with fatigue. Among participants reporting fatigue, 52% had inactive disease and 48% had active disease based on endoscopy whereas 63% reported clinically active disease and 37% reported clinically inactive disease. In the multivariate regression model, clinical disease activity (odds ratio [OR] = 8.5; 95% CI [3.9, 18.6]) and anxiety (OR = 2.8; 95% CI [1.0, 7.6]) were significantly associated with fatigue. The prevalence of fatigue is high among individuals with active and inactive disease. Clinical disease activity and anxiety, but not endoscopic disease activity, were associated with fatigue.
International Survey of Clinical Monitoring Practices in Pancreas and Islet Transplantation
Authors: Ward Casey , Odorico Jon S. , Rickels Michael R. , Berney Thierry , Burke George W. , Kay Thomas W.H. , Thaunat Olivier , Uva Pablo D. , de Koning Eelco J.P. , Arbogast Helmut , Scholz Hanne , Cattral Mark S. , Stratta Robert J. , Stock Peter G. ,   for the International Pancreas and Islet Transplant Association Beta-Cell Replacement Therapy Monitoring Task Force
Published: January 2022

Background.

The long-term outcomes of both pancreas and islet allotransplantation have been compromised by difficulties in the detection of early graft dysfunction at a time when a clinical intervention can prevent further deterioration and preserve allograft function. The lack of standardized strategies for monitoring pancreas and islet allograft function prompted an international survey established by an International Pancreas and Islet Transplant Association/European Pancreas and Islet Transplant Association working group.

Methods.

A global survey was administered to 24 pancreas and 18 islet programs using Redcap. The survey addressed protocolized and for-cause immunologic and metabolic monitoring strategies following pancreas and islet allotransplantation. All invited programs completed the survey.

Results.

The survey identified that in both pancreas and islet allograft programs, protocolized clinical monitoring practices included assessing body weight, fasting glucose/C-peptide, hemoglobin A1c, and donor-specific antibody. Protocolized monitoring in islet transplant programs relied on the addition of mixed meal tolerance test, continuous glucose monitoring, and autoantibody titers. In the setting of either suspicion for rejection or serially increasing hemoglobin A1c/fasting glucose levels postpancreas transplant, Doppler ultrasound, computed tomography, autoantibody titers, and pancreas graft biopsy were identified as adjunctive strategies to protocolized monitoring studies. No additional assays were identified in the setting of serially increasing hemoglobin A1c levels postislet transplantation.

Conclusions.

This international survey identifies common immunologic and metabolic monitoring strategies utilized for protocol and for cause following pancreas and islet transplantation. In the absence of any formal studies to assess the efficacy of immunologic and metabolic testing to detect early allograft dysfunction, it can serve as a guidance document for developing monitoring algorithms following beta-cell replacement.
The microdynamics shaping the relationship between democracy and corruption
Authors: Podobnik Boris , Jusup Marko , Korošak Dean , Holme Petter , Lipić Tomislav
Published: January 2022

Physics has a long tradition of laying rigorous quantitative foundations for social phenomena. Here, we up the ante for physics' forays into the territory of social sciences by (i) empirically documenting a tipping point in the relationship between democratic norms and corruption suppression, and then (ii) demonstrating how such a tipping point emerges from a micro-scale mechanistic model of spin dynamics in a complex network. Specifically, the tipping point in the relationship between democratic norms and corruption suppression is such that democratization has little effect on suppressing corruption below a critical threshold, but a large effect above the threshold. The micro-scale model of spin dynamics underpins this phenomenon by reinterpreting spins in terms of unbiased (i.e. altruistic) and biased (i.e. parochial) other-regarding behaviour, as well as the corresponding voting preferences. Under weak democratic norms, dense social connections of parochialists enable coercing enough opportunist voters to vote in favour of perpetuating parochial in-group bias. Society may, however, strengthen democratic norms in a rapid turn of events during which opportunists adopt altruism and vote to subdue bias. The emerging model outcome at the societal scale thus mirrors the data, implying that democracy either perpetuates or suppresses corruption depending on the prevailing democratic norms.
Aquatic surface respiration improves survival during hypoxia in zebrafish (Danio rerio) lacking hypoxia-inducible factor 1-α
Authors: Mandic Milica , Flear Kaitlyn , Qiu Pearl , Pan Yihang K. , Perry Steve F. , Gilmour Kathleen M.
Published: January 2022

Hypoxia-inducible factor 1-α (Hif-1α), an important transcription factor regulating cellular responses to reductions in O2, previously was shown to improve hypoxia tolerance in zebrafish (Danio rerio). Here, we examined the contribution of Hif-1α to hypoxic survival, focusing on the benefit of aquatic surface respiration (ASR). Wild-type and Hif-1α knockout lines of adult zebrafish were exposed to two levels (moderate or severe) of intermittent hypoxia. Survival was significantly compromised in Hif-1α knockout zebrafish prevented from accessing the surface during severe (16 mmHg) but not moderate (23 mmHg) hypoxia. When allowed access to the surface in severe hypoxia, survival times did not differ between wild-type and Hif-1α knockouts. Performing ASR mitigated the negative effects of the loss of Hif-1α with the knockouts initiating ASR at a higherPO2threshold and performing ASR for longer than wild-types. The loss of Hif-1α had little impact on survival in fish between 1 and 5 days post-fertilization, but as the larvae aged, their reliance on Hif-1α increased. Similar to adult fish, ASR compensated for the loss of Hif-1α on survival. Together, these results demonstrate that age, hypoxia severity and, in particular, the ability to perform ASR significantly modulate the impact of Hif-1α on survival in hypoxic zebrafish.
Catching the virus – a peer-to-peer game that encourages active participation in microbiology lectures
Authors: Dean Paul
Published: January 2022

An important part of learning within lectures and classrooms is active participation, but this is sometimes difficult in larger lecture rooms. Questioning students is also not very fruitful in larger rooms for many reasons and invariably results in a wall of silence. Playing active-learning games changes the student–teacher dynamic and energizes the lecture room, making the lecture more memorable and worthwhile for the students. In our microbiological lectures, particularly lectures on virology and immunology, students play the ‘catch-the-virus’ game. As all students are in the game together, there is a competitive edge, and students forget about the anxiety of the the lecture theatre. Importantly, because of the nature of the game, the entire lecture room is involved, including students in the back rows. Interestingly, the recent coronavirus disease 2019 (COVID-19) pandemic, and its impact on student lives, makes the catch-a-virus game even more poignant.
Evolution of two-component quorum sensing systems
Authors: Giannakara Marina , Koumandou Vassiliki Lila
Published: January 2022

Quorum sensing (QS) is a cell-to-cell communication system that enables bacteria to coordinate their gene expression depending on their population density, via the detection of small molecules called autoinducers. In this way bacteria can act collectively to initiate processes like bioluminescence, virulence and biofilm formation. Autoinducers are detected by receptors, some of which are part of two-component signal transduction systems (TCS), which comprise of a (usually membrane-bound) sensor histidine kinase (HK) and a cognate response regulator (RR). Different QS systems are used by different bacterial taxa, and their relative evolutionary relationships have not been extensively studied. To address this, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to identify all the QS HKs and RRs that are part of TCSs and examined their conservation across microbial taxa. We compared the combinations of the highly conserved domains in the different families of receptors and response regulators using the Simple Modular Architecture Research Tool (SMART) and KEGG databases, and we also carried out phylogenetic analyses for each family, and all families together. The distribution of the different QS systems across taxa, indicates flexibility in HK–RR pairing and highlights the need for further study of the most abundant systems. For both the QS receptors and the response regulators, our results indicate close evolutionary relationships between certain families, highlighting a common evolutionary history which can inform future applications, such as the design of novel inhibitors for pathogenic QS systems.
Accurate sex classification from neural responses to sexual stimuli
Authors: Putkinen Vesa , Nazari-Farsani Sanaz , Karjalainen Tomi , Santavirta Severi , Hudson Matthew , Seppälä Kerttu , Sun Lihua , Karlsson Henry K. , Hirvonen Jussi , Nummenmaa Lauri
Published: January 2022

Sex differences in brain activity evoked by sexual stimuli remain elusive despite robust evidence for stronger enjoyment of and interest towards sexual stimuli in men than in women. To test whether visual sexual stimuli evoke different brain activity patterns in men and women, we measured haemodynamic brain activity induced by visual sexual stimuli in two experiments in 91 subjects (46 males). In one experiment, the subjects viewed sexual and non-sexual film clips and dynamic annotations for nudity in the clips was used to predict their hemodynamic activity. In the second experiment, the subjects viewed sexual and non-sexual pictures in an event-related design. Males showed stronger activation than females in the visual and prefrontal cortices and dorsal attention network in both experiments. Furthermore, using multivariate pattern classification we could accurately predict the sex of the subject on the basis of the brain activity elicited by the sexual stimuli. The classification generalized across the experiments indicating that the sex differences were consistent. Eye tracking data obtained from an independent sample of subjects (N = 110) showed that men looked longer than women at the chest area of the nude female actors in the film clips. These results indicate that visual sexual stimuli evoke discernible brain activity patterns in men and women which may reflect stronger attentional engagement with sexual stimuli in men than women.
Insights into the structure and function of the human organic anion transporter 1 in lipid bilayer membranes
Authors: Janaszkiewicz Angelika , Tóth Ágota , Faucher Quentin , Martin Marving , Chantemargue Benjamin , Guellec Chantal Barin-Le , Marquet Pierre , Di Meo Florent
Published: January 2022

The human SLC22A6/OAT1 plays an important role in the elimination of a broad range of endogenous substances and xenobiotics thus attracting attention from the pharmacological community. Furthermore, OAT1 is also involved in key physiological events such as the remote inter-organ communication. Despite its significance, the knowledge about hOAT1 structure and the transport mechanism at the atomic level remains fragmented owing to the lack of resolved structures. By means of protein-threading modeling refined by μs-scaled Molecular Dynamics simulations, the present study provides the first robust model of hOAT1 in outward-facing conformation. Taking advantage of the AlphaFold 2 predicted structure of hOAT1 in inward-facing conformation, we here provide the essential structural and functional features comparing both states. The intracellular motifs conserved among Major Facilitator Superfamily members create a so-called “charge-relay system” that works as molecular switches modulating the conformation. The principal element of the event points at interactions of charged residues that appear crucial for the transporter dynamics and function. Moreover, hOAT1 model was embedded in different lipid bilayer membranes highlighting the crucial structural dependence on lipid-protein interactions. MD simulations supported the pivotal role of phosphatidylethanolamine components to the protein conformation stability. The present model is made available to decipher the impact of any observed polymorphism and mutation on drug transport as well as to understand substrate binding modes.
Cell surface receptor kinase FERONIA linked to nutrient sensor TORC signaling controls root hair growth at low temperature linked to low nitrate inArabidopsis thaliana
Authors: Martínez Pacheco Javier , Song Limei , Kuběnová Lenka , Ovečka Miroslav , Gabarain Victoria Berdion , Peralta Juan Manuel , Lehuedé Tomás Urzúa , Ibeas Miguel Angel , Ricardi Martiniano M. , Zhu Sirui , Shen Yanan , Schepetilnikov Mikhail , Ryabova Lyubov A , Alvarez José M. , Gutierrez Rodrigo A. , Grossman Guido , Šamaj Jozef , Yu Feng , Estevez José M.
Published: January 2022

Root hairs (RH) are excellent model systems for studying cell size and polarity since they elongate several hundred-fold their original size. Their tip growth is determined both by intrinsic and environmental signals. Although nutrient availability and temperature are key factors for a sustained plant growth, the molecular mechanisms underlying their sensing and downstream signaling pathways remain unclear. Here, we identified that low temperature (10°C) triggers a strong RH elongation response involving the cell surface receptor kinase FERONIA (FER) and the nutrient sensing TOR Complex 1 (TORC). In this study, we found that FER is required to perceive limited nutrient availability caused by low temperature. FER interacts with and activates TORC downstream components to trigger RH growth. In addition, the small GTPase Rho-related protein from plants 2 (ROP2) is also involved in this RH growth response linking FER and TOR. We also found that limited nitrogen nutrient availability can mimic the RH growth response at 10°C in a NRT1.1-dependent manner. These results uncover a molecular mechanism by which a central hub composed by FER-ROP2-TORC is involved in the control of RH elongation under low temperature and nitrogen deficiency.
Pervasive conditional selection of driver mutations and modular epistasis networks in cancer
Authors: Iranzo Jaime , Gruenhagen George , Calle-Espinosa Jorge , Koonin Eugene V.
Published: January 2022

Cancer driver mutations often display mutual exclusion or co-occurrence, underscoring the key role of epistasis in carcinogenesis. However, estimating the magnitude of epistasis and quantifying its effect on tumor evolution remains a challenge. We developed a method to quantify COnditional SELection on the Excess of Nonsynonymous Substitutions (Coselens) in cancer genes. Coselens infers the number of drivers per gene in different partitions of a cancer genomics dataset using covariance-based mutation models and determines whether coding mutations in a gene affect selection for drivers in any other gene. Using Coselens, we identified 296 conditionally selected gene pairs across 16 cancer types in the TCGA dataset. Conditional selection affects 25-50% of driver substitutions in tumors with >2 drivers. Conditionally co-selected genes form modular networks, whose structures challenge the traditional interpretation of within-pathway mutual exclusivity and across-pathway synergy, suggesting a more complex scenario, where gene-specific across-pathway epistasis shapes differentiated cancer subtypes.
Head Removal Enhances Planarian Electrotaxis
Authors: Sabry Ziad , Wang Rui , Jahromi Aryo , Rabeler Christina , Kristan William B. , Collins Eva-Maria S.
Published: January 2022

Sensing electric fields is an ability that certain animal species utilize for communication, hunting, and spatial orientation. Freshwater planarians move toward the cathode in a static electric field (cathodic electrotaxis). First described by Raymond Pearl more than a century ago, planarian electrotaxis has received little attention and the underlying mechanisms and evolutionary significance remain unknown. We developed an apparatus and scoring metrics for automated quantitative and mechanistic studies of planarian behavior upon exposure to a static electric field. Using this automated setup, we characterized electrotaxis in the planarian Dugesia japonica and found that this species responds to voltage instead of to current, in contrast to results from previous studies using other species. Because longer planarians exhibited more robust electrotaxis than shorter planarians, we hypothesized that signals from the head impede cathodic electrotaxis. To test this hypothesis, we took advantage of the regenerative abilities of planarians and compared electrotaxis in head and tail fragments of various lengths. We found that tail and trunk fragments electrotaxed while head fragments did not, regardless of size. However, we could restore cathodic electrotaxis in head fragments via decapitation, demonstrating that the presence of the head impaired cathodic electrotaxis. This result is in stark contrast to other stimulated behaviors such as phototaxis, thermotaxis or chemotaxis, which are weaker or absent in headless fragments. Thus, electrotaxis may be an important ability of headless planarian fragments to support survival prior to head regeneration.

Summary statement

We present a new method for quantitative studies of planarian electrotaxis and show that Dugesia japonica move toward the cathode. This behavior is enhanced by removal of the head.