bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiparametric magnetic resonance imaging allows non-invasive functional and structural evaluation of diabetic kidney disease
Authors: Makvandi Kianoush , Hockings Paul D , Jensen Gert , Unnerstall Tim , Leonhardt Henrik , Jarl Lisa V , Englund Camilla , Francis Susan , Sundgren Anna K , Hulthe Johannes , Baid-Agrawal Seema
Published: February 2022

Background

We sought to develop a novel non-contrast multiparametric MRI (mpMRI) protocol employing several complementary techniques in a single scan session for a comprehensive functional and structural evaluation of diabetic kidney disease (DKD).

Methods

In the cross-sectional part of this prospective observational study, 38 subjects ages 18‒79 years with type 2 diabetes and DKD [estimated glomerular filtration rate (eGFR) 15‒60 mL/min/1.73 m2] and 20 age- and gender-matched healthy volunteers (HVs) underwent mpMRI. Repeat mpMRI was performed on 23 DKD subjects and 10 HVs. By measured GFR (mGFR), 2 DKD subjects had GFR stage G2, 16 stage G3 and 20 stage G4/G5. A wide range of MRI biomarkers associated with kidney haemodynamics, oxygenation and macro/microstructure were evaluated. Their optimal sensitivity, specificity and repeatability to differentiate diabetic versus healthy kidneys and categorize various stages of disease as well as their correlation with mGFR/albuminuria was assessed.

Results

Several MRI biomarkers differentiated diabetic from healthy kidneys and distinct GFR stages (G3 versus G4/G5); mean arterial flow (MAF) was the strongest predictor (sensitivity 0.94 and 1.0, specificity 1.00 and 0.69; P = .04 and .004, respectively). Parameters significantly correlating with mGFR were specific measures of kidney haemodynamics, oxygenation, microstructure and macrostructure, with MAF being the strongest univariate predictor (r = 0.92; P < .0001).

Conclusions

A comprehensive and repeatable non-contrast mpMRI protocol was developed that, as a single, non-invasive tool, allows functional and structural assessment of DKD, which has the potential to provide valuable insights into underlying pathophysiology, disease progression and analysis of efficacy/mode of action of therapeutic interventions in DKD.
A case report—facing blues in cardiac amyloidosis: no more a zebra
Authors: Nath Ranjit Kumar , Shrivastava Abhinav
Published: February 2022

Background

Cardiac amyloidosis presentation in an affected individual can be varied. We describe a patient who had the entire spectrum of involvement in his life time. Initially presented as an ischaemic heart disease and later developed complete heart block (CHB) and frank cardiomyopathy. Increased load of amyloid caused lead-tissue interface disruption resulting in high pacing thresholds with difficulty in capture during permanent pacemaker implantation requiring a novel strategy of management.

Case summary

A 65-year-old male presented with two episodes of syncope with a history of gradually progressive dyspnoea of 6 months duration along with lower limb swelling for last 1–2 months. He had a history of drug-eluting stent implantation for stable ischaemic heart disease 4 years back. Now he presented with a CHB and a transthoracic echocardiogram hinted towards a restrictive physiology and an infiltrative disease. Cardiac magnetic resonance imaging could not be done in view of the incompatible temporary pacemaker on which the patient was dependent. Abdominal fat pad biopsy was positive for amyloid. He was taken up for permanent pacemaker implantation; however, multiple attempts could not achieve desired threshold and capture amplitudes in the right ventricular apex, septum, or outflow region. The lead was placed in the coronary sinus and a stent was placed proximally to trap the lead behind the deployed stent. Threshold and impedance were satisfactory. Cardiac biopsy subsequently confirmed aTTR amyloidosis.

Discussion

The patient had an ischaemic heart disease, conduction disease, and cardiomyopathy as the manifestation of cardiac amyloidosis. While two-dimensional echo is the screening tool of choice, cardiac biopsy remains the gold standard of diagnosis for amyloidosis. Cardiac pacing comes with its own unique set of challenges in patients with advanced amyloid cardiomyopathy and have to be overcome for symptomatic benefit of the patient. Coronary sinus may be utilized in such patients for single-site ventricular pacing and placing a stent may help to anchor the lead when placed within it.
Global disparities in prescription of guideline-recommended drugs for heart failure with reduced ejection fraction
Authors: Tromp Jasper , Ouwerkerk Wouter , Teng Tiew-Hwa K , Cleland John G F , Bamadhaj Sahiddah , Angermann Christiane E , Dahlstrom Ulf , Tay Wan Ting , Dickstein Kenneth , Ertl Georg , Hassanein Mahmoud , Perrone Sergio V , Ghadanfar Mathieu , Schweizer Anja , Obergfell Achim , Collins Sean P , Filippatos Gerasimos , Lam Carolyn S P
Published: February 2022

Background

Heart failure (HF) is a global challenge, with lower- and middle-income countries (LMICs) carrying a large share of the burden. Treatment for HF with reduced ejection fraction (HFrEF) improves survival but is often underused. Economic factors might have an important effect on the use of medicines.

Methods and results

This analysis assessed prescription rates and doses of renin–angiotensin system (RAS) inhibitors, β-blockers, and mineralocorticoid receptor antagonists at discharge and 6-month follow-up in 8669 patients with HFrEF (1458 from low-, 3363 from middle-, and 3848 from high-income countries) hospitalized for acute HF in 44 countries in the prospective REPORT-HF study. We investigated determinants of guideline-recommended treatments and their association with 1-year mortality, correcting for treatment indication bias.

Only 37% of patients at discharge and 34% of survivors at 6 months were on all three medication classes, with lower proportions in LMICs than high-income countries (19 vs. 41% at discharge and 15 vs. 37% at 6 months). Women and patients without health insurance, or from LMICs, or without a scheduled medical follow-up within 6 months of discharge were least likely to be on guideline-recommended medical therapy at target doses, independent of confounders. Being on ≥50% of guideline-recommended doses of RAS inhibitors, and β-blockers were independently associated with better 1-year survival, regardless of country income level.

Conclusion

Patients with HFrEF in LMICs are less likely to receive guideline-recommended drugs at target doses. Improved access to medications and medical care could reduce international disparities in outcome.
Changes in the phyllosphere and rhizosphere microbial communities of soybean in the presence of pathogens
Authors: Díaz-Cruz Gustavo A , Cassone Bryan J
Published: February 2022

Soybean (Glycine max L.) is host to an array of foliar- and root-infecting pathogens that can cause significant yield losses. To provide insights into the roles of microorganisms in disease development, we evaluated the bacterial and fungal communities associated with the soybean rhizosphere and phyllosphere. For this, leaf and soil samples of healthy, Phytophthora sojae-infected and Septoria glycines-infected plants were sampled at three stages during the production cycle, and then subjected to 16S and Internal Transcribed Spacer (ITS) amplicon sequencing. The results indicated that biotic stresses did not have a significant impact on species richness and evenness regardless of growth stage. However, the structure and composition of soybean microbial communities were dramatically altered by biotic stresses, particularly for the fungal phyllosphere. Additionally, we cataloged a variety of microbial genera that were altered by biotic stresses and their associations with other genera, which could serve as biological indicators for disease development. In terms of soybean development, the rhizosphere and phyllosphere had distinct microbial communities, with the fungal phyllosphere most influenced by growth stage. Overall, this study characterized the phyllosphere and rhizosphere microbial communities of soybean, and described the impact of pathogen infection and plant development in shaping these bacterial and fungal communities.
A Mixed-methods Assessment of the Impact of Insurance Issues on the Emotional and Physical Health of Patients With Inflammatory Bowel Disease
Authors: Philippou Alicia , Birhanu Beselot , Biello Anthony , Keefer Laurie , Gorbenko Ksenia
Published: February 2022

Background

In patients with inflammatory bowel disease (IBD), failure to adhere to treatment regimens due to insurance issues can lead to disease complications. Our aim was to examine patients’ perceptions of the impact of insurance issues on their health.

Methods

Twenty-nine patients with IBD at a large US academic center and an insurance issue participated in a mixed-methods study. Retrospective chart review and an online questionnaire were completed to collect demographic information, IBD characteristics, and validated resilience scores. Semistructured interviews were completed for insurance experiences, which were coded independently by 2 coders for themes.

Results

Twenty-nine patients completed the interview, and 24 completed the online survey. Sixteen had Crohn’s disease, 13 had ulcerative colitis, and 66% were female. The most common insurance issue was lapsed insurance. Many experienced physical consequences, with 58% having flares, 14% undergoing surgery, and 14% developing antibodies. All emotional responses were negative, with the majority feeling stressed (38%). Providers were uninformed of insurance issues in 28% of cases. When asked about perceived resilience, 41% felt incapable of managing the situation, and 45% gave up trying to solve the problem. When asked how to improve going forward, 38% requested an easily accessible advocate to guide them.

Conclusions

A large proportion of our cohort chose not to inform their provider, felt incapable of managing on their own, and gave up on resolving their insurance issue. This highlights the need to consider restructuring the insurance system, to identify those at risk for insurance issues, and to make advocates available to avoid devastating consequences.
Heavy metals in the blueband hermit crab, Pagurus samuelis (Stimpson, 1857) (Decapoda: Anomura: Paguridae), from two Southern California habitats
Authors: dos Santos Tyler S , Boskovic Danilo S , Shih Wendy , Dunbar Stephen G
Published: February 2022

Although heavy metal concentrations naturally vary in the environment, anthropogenic sources of heavy metals can mask and override such fluctuations. Indicator species can be used to determine environmental concentrations of certain metals and evaluate the impacts of metals from associated anthropogenic sources. We sought to determine if the hermit crab Pagurus samuelis (Stimpson, 1857) may play a role as an indicator species along the Southern California coast. Seawater and P. samuelis samples were collected from both Cabrillo Beach and White Point Beach rocky intertidal locations and analyzed for concentrations of cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), and zinc (Zn) using microwave plasma-atomic emission spectrometry (MP-AES). Lead concentrations were higher in seawater at Cabrillo Beach compared to White Point Beach, whereas Zn concentrations were higher at White Point Beach than at Cabrillo Beach. All other metals were not significantly different between these locations. Cd was higher in hermit crabs collected from Cabrillo Beach than those from White Point Beach, whereas Cr was higher in crabs collected from White Point Beach compared with those from Cabrillo Beach. In comparisons of seawater with samples of hermit crabs, seawater had higher concentrations of Zn and Cd, whereas hermit crabs had higher concentrations of Cu at both locations, and higher levels of Cr at White Point Beach. While this study does not provide conclusive evidence that P. samuelis is an indicator species, it does demonstrate differences in metal concentrations between tested locations and populations of P. samuelis. Although P. samuelis may not be negatively impacted by the heavy metal concentrations we found, the risks of potential bioaccumulation at higher trophic levels is of concern.
Prognostic Relevance of Transforming Growth Factor-β Receptor Expression and Signaling in Glioblastoma, Isocitrate Dehydrogenase-Wildtype
Authors: Togni Claudio , Rom Emanuel , Burghardt Isabel , Roth Patrick , Rushing Elisabeth J , Weller Michael , Gramatzki Dorothee
Published: February 2022

The transforming growth factor (TGF)-β signaling pathway has been recognized as a major factor in promoting the aggressive behavior of glioblastoma, isocitrate dehydrogenase-wildtype. However, there is little knowledge about the expression of TGF-β receptors in glioblastoma. Here, we studied the expression patterns of TGF-β receptor II (TGFβRII), type I receptors activin receptor-like kinase (ALK)-5, and ALK-1, as well as of the transcriptional regulators inhibitor of differentiation (Id) 2, Id3, and Id4 in human glioblastoma. The expression of TGFβRII, ALK-5, and ALK-1 varied greatly, with TGFβRII and ALK-5 being the most abundant and ALK-1 being the least expressed receptor. None of the 3 receptors was preferentially expressed by tumor vasculature as opposed to the tumor bulk, indicating tumor bulk-governed mechanisms of TGF-β signaling with regard to glioblastoma-associated angiogenesis. A positive correlation was found between ALK-1 and Id2, suggesting that Id2, broadly expressed in the tumor cells, is a downstream target of this receptor-dependent pathway. Furthermore, there was a trend for high expression of ALK-5 or Id2 to be associated with inferior overall survival. Hence, we propose that ALK-5 may be used for patient stratification in future anti-TGF-β treatment trials and that Id2 might be a potential target for anti-TGF-β interventions.
Effects of internal exposure to neutron-activated 56MnO2 powder on locomotor activity in rats
Authors: Otani Keiko , Ohtaki Megu , Fujimoto Nariaki , Uzbekov Darkhan , Kairkhanova Ynkar , Saimova Aisulu , Chaizhunusova Nailya , Habdarbaeva Dariya , Azhimkhanov Almas , Zhumadilov Kassym , Stepanenko Valeriy , Hoshi Masaharu
Published: February 2022

At the detonation of the atomic bombing in Hiroshima and Nagasaki, a significant amount of radionuclides was produced by the neutron induced activation. The residual radiation from the explosion is crucial to the health risk of the people who entered these cities after the bombing and might have inhaled these radioactive materials. Because 56Mn is one of the major radionuclides produced in soil and have not been studied until now, we had conducted a series of experiments using rats to investigate the biological impacts of exposure of 56MnO2 particles. In these experiments, the rats’ spontaneous locomotor activity was also assessed to examine the possible effects of 56Mn on their behavior. However, the locomotor activity data obtained from an individual experiment failed to identify radiation effects due to the large variation among animals and the small sample size. In the present study, all available data from our previous studies on 56MnO2 exposure (0.02–0.15 Gy of whole-body doses) as well as 60Co-γ exposure (at 2–5 Gy of whole-body doses) were pooled. Our statistical method, which takes into account individual differences and daily fluctuations, successfully identified a decrease in locomotor activity caused by 56MnO2 exposure, where the changes were gradual and reached the maximum reduction around 2 weeks after exposure. In contrast, exposure to 60Co-γ rays produced the highest decline of activity within one day. These results suggest that internal exposure to 56Mn at whole-body doses of even less than 0.15 Gy may have a long-lasting impact on locomotor activity.
Considering the market share of vaccines against tick-borne encephalitis reported in Austria
Authors: Jenkins Victoria A , Hoet Bernard
Published: February 2022

Different market share values for TBE vaccines in Austria are reported during the period 2018–2020. However, both data likely cover a significant under-estimation of doses distributed. Thus, for epidemiological evaluations, market share should be used with prudence and only reported when solid whole-market market share can be validated and referenced.
Serratia marcescensPLR enhances lateral root formation through supplying PLR-derived auxin and enhancing auxin biosynthesis in Arabidopsis
Authors: Zhang Chunlei , Yu Zipeng , Zhang Mengyue , Li Xiaoxuan , Wang Mingjing , Li Lixin , Li Xugang , Ding Zhaojun , Tian Huiyu
Published: February 2022

Plant growth promoting rhizobacteria (PGPR) refer to bacteria that colonize the rhizosphere and contribute to plant growth or stress tolerance. To further understand the molecular mechanism by which PGPR exhibit symbiosis with plants, we performed a high-throughput single colony screening from the rhizosphere, and uncovered a bacterium (named promoting lateral root, PLR) that significantly promotes Arabidopsis lateral root formation. By 16S rDNA sequencing, PLR was identified as a novel sub-species of Serratia marcescens. RNA-seq analysis of Arabidopsis integrated with phenotypic verification of auxin signalling mutants demonstrated that the promoting effect of PLR on lateral root formation is dependent on auxin signalling. Furthermore, PLR enhanced tryptophan-dependent indole-3-acetic acid (IAA) synthesis by inducing multiple auxin biosynthesis genes in Arabidopsis. Genome-wide sequencing of PLR integrated with the identification of IAA and its precursors in PLR exudates showed that tryptophan treatment significantly enhanced the ability of PLR to produce IAA and its precursors. Interestingly, PLR induced the expression of multiple nutrient (N, P, K, S) transporter genes in Arabidopsis in an auxin-independent manner. This study provides evidence of how PLR enhances plant growth through fine-tuning auxin biosynthesis and signalling in Arabidopsis, implying a potential application of PLR in crop yield improvement through accelerating root development.
FRB 121102: Drastic changes in the burst polarization contrasts with the stability of the persistent emission
Authors: Plavin A , Paragi Z , Marcote B , Keimpema A , Hessels J W T , Nimmo K , Vedantham H K , Spitler L G
Published: February 2022

We study milliarcsecond-scale properties of the persistent radio counterpart to FRB 121102 and investigate the spectro-polarimetric properties of a bright burst. For the former, we use European VLBI Network (EVN) observations in 2017 at 1.7 and 4.8 GHz. For the latter, we reanalyse the 1.7-GHz data from the 100-m Effelseberg telescope taken in 2016. These observations predate other polarimetric studies of FRB 121102, and yield the highest burst Faraday rotation measure (RM) to date, RM = 1.27 · 105 rad m−2, consistent with the decreasing RM trend. The fractional polarization of the burst emission is 15 per cent at 1.7 GHz. This can be reconciled with the high-fractional polarization at higher frequencies if the Faraday width of the burst environment is 150 rad m−2 – a bare 0.1 per cent of the total Faraday rotation. The width may originate from minor non-uniformities in the Faraday screen, or from effects in the emitting region itself. The upper limit on the persistent source size is 1 pc, barely consistent with a young supernova (SN) scenario. The flux variability limit of $\lt 10{{\ \rm per\ cent}}$ is not in favour of the young SN scenario, and challenges other interpretations as well. The fractional polarization of the faint persistent source is constrained at $\lt 25{{\ \rm per\ cent}}$ at 4.8 GHz ruling out a common origin with the highly polarized individual bursts.
Antispacer peptide nucleic acids for sequence-specific CRISPR-Cas9 modulation
Authors: Economos Nicholas G , Quijano Elias , Carufe Kelly E W , Perera J Dinithi R , Glazer Peter M
Published: February 2022

Despite the rapid and broad implementation of CRISPR-Cas9-based technologies, convenient tools to modulate dose, timing, and precision remain limited. Building on methods using synthetic peptide nucleic acids (PNAs) to bind RNA with unusually high affinity, we describe guide RNA (gRNA) spacer-targeted, or ‘antispacer’, PNAs as a tool to modulate Cas9 binding and activity in cells in a sequence-specific manner. We demonstrate that PNAs rapidly and efficiently target complexed gRNA spacer sequences at low doses and without design restriction for sequence-selective Cas9 inhibition. We further show that short PAM-proximal antispacer PNAs achieve potent cleavage inhibition (over 2000-fold reduction) and that PAM-distal PNAs modify gRNA affinity to promote on-target specificity. Finally, we apply antispacer PNAs for temporal regulation of two dCas9-fusion systems. These results present a novel rational approach to nucleoprotein engineering and describe a rapidly implementable antisense platform for CRISPR-Cas9 modulation to improve spatiotemporal versatility and safety across applications.
ZMYM2 restricts 53BP1 at DNA double-strand breaks to favor BRCA1 loading and homologous recombination
Authors: Lee Doohyung , Apelt Katja , Lee Seong-Ok , Chan Hsin-Ru , Luijsterburg Martijn S , Leung Justin W C , Miller Kyle M
Published: February 2022

An inability to repair DNA double-strand breaks (DSBs) threatens genome integrity and can contribute to human diseases, including cancer. Mammalian cells repair DSBs mainly through homologous recombination (HR) and nonhomologous end-joining (NHEJ). The choice between these pathways is regulated by the interplay between 53BP1 and BRCA1, whereby BRCA1 excludes 53BP1 to promote HR and 53BP1 limits BRCA1 to facilitate NHEJ. Here, we identify the zinc-finger proteins (ZnF), ZMYM2 and ZMYM3, as antagonizers of 53BP1 recruitment that facilitate HR protein recruitment and function at DNA breaks. Mechanistically, we show that ZMYM2 recruitment to DSBs and suppression of break-associated 53BP1 requires the SUMO E3 ligase PIAS4, as well as SUMO binding by ZMYM2. Cells deficient for ZMYM2/3 display genome instability, PARP inhibitor and ionizing radiation sensitivity and reduced HR repair. Importantly, depletion of 53BP1 in ZMYM2/3-deficient cells rescues BRCA1 recruitment to and HR repair of DSBs, suggesting that ZMYM2 and ZMYM3 primarily function to restrict 53BP1 engagement at breaks to favor BRCA1 loading that functions to channel breaks to HR repair. Identification of DNA repair functions for these poorly characterized ZnF proteins may shed light on their unknown contributions to human diseases, where they have been reported to be highly dysregulated, including in several cancers.
Âcimowin Waspison: Cultivating curiosity, sharing stories, and taking steps forward in Canada’s ‘Calls to Action’
Authors: MacNairn Ian Adam Smith , Al-Ani Abdullah
Published: February 2022

We have yet to fully walk the path of the Calls to Action put forth by the Truth & Reconciliation Commission of Canada within our health care system. In this piece, we offer a suggestion of enhanced and increased curiosity and empathy in our practice as health care providers, particularly in regard to Call 22. This encouragement is exemplified through sharing learning we received around an Indigenous way of knowing and traditional health practice: waspison, known in English as, ‘moss bag’. Waspison is a sacred prenatal and postnatal practice used since time immemorial and carrying through to today, across Canada and the USA. It is a novel teaching example not previously discussed in medical literature. Our intention is to stoke greater interest in practicing deep caring for our patients in ways that are culturally humble, safe, and as competent as possible. That is, learning more about our patients through curiosity and empathy.
The Impact of Active Bystander Training on Officer Confidence and Ability to Address Ethical Challenges
Authors: Taniguchi Travis , Vovak Heather , Cordner Gary , Amendola Karen , Yang Yukun , Hoogesteyn Katherine , Bartness Martin
Published: February 2022

Active bystandership (AB) training in the Baltimore Police Department (titled Ethical Policing is Courageous, (EPIC)) was designed to (1) prevent misconduct, (2) avoid mistakes, and (3) promote healthy officers. AB training promotes an organizational culture where officers feel empowered to intervene when noticing their colleagues are or are about to, engage in dangerous, unwanted, or inappropriate behaviour. It focuses on direct intervention in an informal capacity rather than formalized reporting. Self-report surveys (n = 1,753) were collected immediately post-completion of EPIC training. Survey domains included perceived impact of the training on behaviour, application to the job, confidence in ability to intervene, and ability to address ethical challenges. A large majority of respondents indicated greater likelihood of intervening after the training and having confidence in their ability to intervene with peers and supervisors; write-in responses suggested that the biggest perceived challenge was in intervening with supervisors.
Post-COVID-19 HSV encephalitis: a review
Authors: Gupta S , Dutta A , Chakraborty U , Kumar R , Das D , Ray B K
Published: February 2022

Background

Herpes simplex virus encephalitis (HSVE) is one of the most common infectious causes of sporadic encephalitis. Coronavirus disease (COVID-19) has been associated with immune dysregulation of the host that might increase the risk of infections like HSVE following SARS-CoV-2 infection. There is paucity of literature on post COVID-19 HSVE. This study was conducted with the aim of analyzing the clinical presentation, brain imaging, and outcome of patients presenting with HSVE within 6 weeks of COVID-19 and providing a comprehensive review on the possible mechanisms of post-COVID-19 HSVE.

Methods

This observational study included patients who had laboratory-confirmed HSVE (type 1 or type 2) and a history of COVID-19 within the previous 6 weeks. Patients were followed up for 3 months.

Results

Eight patients were included and all of them had type 1 HSVE. The mean latency of onset of neurological symptoms from being diagnosed with COVID-19 is 23.87 days and a majority of the patients have received injectable steroids with a mean duration of 6.5 days. Behavioral abnormality was the commonest neurological presentation and typical brain imaging involved T2 FLAIR hyperintensities of the medial temporal lobes. All patients received intravenous acyclovir 10 mg/kg every eight hourly for atleast 14 days. One patient with concomitant rhinocerebral mucormycosis succumbed while the majority had a complete recovery.

Conclusion

Possible immune dysregulation in COVID-19 may increase the susceptibility of HSVE in patients with a history of recent SARS-CoV-2 infection. The clinical manifestations and laboratory findings of HSVE in such patients are similar to typical HSVE.
Increased Belief Instability in Psychotic Disorders Predicts Treatment Response to Metacognitive Training
Authors: Hauke D J , Roth V , Karvelis P , Adams R A , Moritz S , Borgwardt S , Diaconescu A O , Andreou C
Published: February 2022

Background and Hypothesis

In a complex world, gathering information and adjusting our beliefs about the world is of paramount importance. The literature suggests that patients with psychotic disorders display a tendency to draw early conclusions based on limited evidence, referred to as the jumping-to-conclusions bias, but few studies have examined the computational mechanisms underlying this and related belief-updating biases. Here, we employ a computational approach to understand the relationship between jumping-to-conclusions, psychotic disorders, and delusions.

Study Design

We modeled probabilistic reasoning of 261 patients with psychotic disorders and 56 healthy controls during an information sampling task—the fish task—with the Hierarchical Gaussian Filter. Subsequently, we examined the clinical utility of this computational approach by testing whether computational parameters, obtained from fitting the model to each individual’s behavior, could predict treatment response to Metacognitive Training using machine learning.

Study Results

We observed differences in probabilistic reasoning between patients with psychotic disorders and healthy controls, participants with and without jumping-to-conclusions bias, but not between patients with low and high current delusions. The computational analysis suggested that belief instability was increased in patients with psychotic disorders. Jumping-to-conclusions was associated with both increased belief instability and greater prior uncertainty. Lastly, belief instability predicted treatment response to Metacognitive Training at the individual level.

Conclusions

Our results point towards increased belief instability as a key computational mechanism underlying probabilistic reasoning in psychotic disorders. We provide a proof-of-concept that this computational approach may be useful to help identify suitable treatments for individual patients with psychotic disorders.
Negotiating Belonging: Race, Class, and Religion in the Brazilian Quest for “Becoming American”
Authors: Serrão Rodrigo
Published: February 2022

This study examines how members of a majority second-generation Brazilian church in South Florida perceive their English-speaking, “American” congregation compared to the Portuguese-speaking Brazilian congregation from which they originated. Data for this research are drawn from in-depth, open-ended interviews with 32 members from different ethnoracial backgrounds, participant observation, and content analysis of the congregations’ social media. Findings show that the discourse of church differences portrays the two congregations in racialized and classist ways. Combining boundary-making and identity work theories, I argue that the perceptions espoused by members of the American congregation come from a place of pressure to assimilate to U.S. White middle-class culture, consequently reinforcing and legitimizing stereotypes in an effort to distance themselves from Brazilian immigrants.
Physician associates in the UK
Authors: Straughton Kate , Roberts Karen A. , Watkins Jeannie , Drennan Vari M. , Halter Mary
Published: February 2022

Physician associates (PAs) have been part of the UK health workforce for almost 20 years. The profession is growing rapidly with statutory regulation, protection of the title, and career progression supported by a national-level framework all in the pipeline for the near future. This article provides a brief history of the profession in the United Kingdom and prospects for its future.
A teaspoon of sugar and a pinch of salt
Authors: Gilbert Brian W. , Dingman J. Spencer , Reeder Jacob A. , Paola Sean Di
Published: February 2022

The traditional hyperosmolar agents used to treat patients with elevated intracranial pressure are mannitol and hypertonic sodium chloride solution. This article focuses on some of the pros and cons of these treatments for managing cerebral edema.
Results in 7 Cases of Neurectomy With a Transverse Plantar Approach for Primary Morton’s Neuroma
Authors: Araujo Espinoza Guillermo , Bazan Alvarez Johannes , Alvarado Zegarra Anibal
Published: February 2022

Surgery is often performed for Morton’s neuroma when conservative treatment is ineffective. This study aimed to describe the surgical results of Morton’s neuroma. Six patients (7 feet) underwent neurectomy via a transverse plantar incision in the forefoot. Changes in perceived pain, function, and patient satisfaction were measured with a Visual Analog Scale, the American Orthopaedic Foot and Ankle Surgery Scale, and the Coughlin score, respectively. Six feet had neuromas in the third intermetatarsal space and 1 foot had neuromas in the third and second spaces. The mean preoperative and postoperative Visual Analog Scale scores were 7.14±0.69 and 1.86±0.69, respectively. The mean preoperative and postoperative American Orthopaedic Foot and Ankle Surgery scores were 69.71±6.73 and 94.86±3.93, respectively. Four patients were very satisfied, and 2 patients were just satisfied. The plantar surgical approach for the treatment of Morton’s neuroma has few complications with good functional results and patient satisfaction in this case series.

Level of Evidence: Diagnostic Level IV—retrospective case series. See Instructions for Authors for a complete description of levels of evidence.
Study of diagnostic value of congenital hypertrophy of retinal pigment epithelium in Chinese familial adenomatous polyposis patients
Authors: Cai Shanrong , Yu Yibo , Xie Xin , Huang Yanqin , Song Yongmao , Zhan Suzhan , Zheng Shu
Published: February 2022

Background

Congenital hypertrophy of retinal pigment epithelium (CHRPE) is an important characteristic of familial adenomatous polyposis (FAP) patients. However, more evidence about its sensitivity, specificity, and diagnostic value for FAP is needed to determine whether CHRPE is a reliable marker.

Methods

Clinical features of FAP patients were investigated using in-person evaluations. Family members of FAP patients were evaluated with an indirect ophthalmoscope to determine whether they had CHRPE. We defined three diagnostic criteria for CHRPE (criteria A, B and C) based on their shape, quantity and size. Those with negative colonoscopy results and gene mutation results were classified as healthy controls.

Results

Of a total of 23 FAP families, 21 families were CHRPE-positive (91.3%). Among those 21 families, 47 individuals had CHRPE, including 33 FAP patients, 9 APC gene mutation carriers, and 5 individuals younger than 18 years who were later confirmed to have FAP. Fifty individuals had no CHRPE (5 FAP patients and 45 individuals without APC gene mutations and colorectal adenoma). The average number of CHRPE lesions per person was 5.81, and CHRPE was located mostly in the posterior pole in the eye fundus; 76.7% of individuals had CHRPE in both eyes. The sensitivity of the three CHRPE criteria ranged from 78.8 to 90.4%, with the highest sensitivity found for criterion A (90.4%), which had a specificity of 100% for healthy controls and sporadic colorectal cancer patients.

Conclusion

CHRPE has vital diagnostic and screening value because of its high sensitivity for discovering FAP and APC gene mutation carriers.
From MAFLD to hepatocellular carcinoma and everything in between
Authors: Bae Sarah Da Won , George Jacob , Qiao Liang
Published: February 2022

Metabolic (dysfunction) associated fatty liver disease (MAFLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease worldwide. Many risk factors contribute to the pathogenesis of MAFLD with metabolic dysregulation being the final arbiter of its development and progression. MAFLD poses a substantial economic burden to societies, which based on current trends is expected to increase over time. Numerous studies have addressed various aspects of MAFLD from its risk associations to its economic and social burden and clinical diagnosis and management, as well as the molecular mechanisms linking MAFLD to end-stage liver disease and hepatocellular carcinoma. This review summarizes current understanding of the pathogenesis of MAFLD and related diseases, particularly liver cancer. Potential therapeutic agents for MAFLD and diagnostic biomarkers are discussed.
Ductal adenocarcinoma of the prostate or seminal vesicle adenocarcinoma: An multi-disciplinary team (MDT) case report and literature review
Authors: Ning Hao , Song Yufeng , Wu Haihu , Gao Dexuan , Lyu Jiaju
Published: February 2022

We introduced a 61-year-old male with ductal adenocarcinoma of the prostate who underwent a tortuous diagnosis and treatment. Multi-disciplinary team meetings organized by our hospital have shown great value in the whole process. The patient presented with gross hematuria accompanied by frequent urination initially, and was diagnosed with ductal adenocarcinoma of the prostate involving right seminal vesicle gland and urethra by urethroscopy biopsy. The clinical stage of tumor was T3bN0M0. After 4 cycles of neoadjuvant chemotherapy, the tumor shrank significantly and the patient underwent a laparoscopic radical prostatectomy. But the patient declined to continue chemotherapy postoperatively. After 10 months, the serum prostatic specific antigen increased to 0.05 ng/mL, and multiple metastases were found in the patient's bilateral lungs. However, an unexpected diagnosis of seminal vesicle adenocarcinoma was put forward from another hospital after supplementary pathologic immunohistochemical examination. Then, after careful discussion and demonstration by our multi-disciplinary team experts, we insisted on the diagnosis of ductal adenocarcinoma of the prostate and suggested that the original regimen of chemotherapy should be continued. Up-to-date, 14 months after the operation, the patient continues to survive while undergoing ongoing active treatment as recommended.
Do recent meta-analyses truly prove that treatment with blood pressure-lowering drugs is beneficial at any blood pressure value, no matter how low? A critical review
Authors: Kreutz Reinhold , Brunström Mattias , Thomopoulos Costas , Carlberg Bo , Mancia Giuseppe
Published: February 2022

Current European guidelines for the management of hypertension and on cardiovascular disease prevention place the threshold for pharmacological treatment at a SBP level of 140 mmHg or above, with the exception of patients at very high risk (mainly because of coronary heart disease). This is in agreement with the current definition of hypertension, that is, the level of blood pressure at which the benefits of treatment outweigh the risks of treatment, as documented by clinical trials. This rationale and definition was recently challenged by meta-analyses using individual participant-level data from 48 randomized trials by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC). The authors calculated for a fixed 5 mmHg pharmacological reduction of SBP an overall 10% risk reduction for major cardiovascular events. It was concluded that there was no reliable evidence of heterogeneity of treatment effects by baseline SBP categories; that the effect was independent from the presence of cardiovascular disease; applied also to old and very old individuals up to 84 years or beyond; and that BP-lowering was also beneficial in individuals with normal or high-normal SBP down to a baseline SBP less than 120 mmHg. In this report, we identify and discuss a number of shortcomings of the BPLTTC meta-analyses. In our view, the conclusions by the BPLTTC must be -together with accompanying suggestions to abandon the definition of hypertension - strongly rejected as they are not justified and may be harmful for cardiovascular health in individuals without hypertension.
Traumatic cataract in a young patient with myopia
Authors: Nuijts Rudy M.M.A. , Ollivier Robin , Kermani Omid , Carones Francesco , Findl Oliver , Aramberri Jaime , Alió Jorge , Reus Nic J. , Rosen Paul
Published: February 2022

A 36-year-old man was referred to our clinic because of traumatic cataract in his right eye, which had developed after being hit in the eye with a badminton shuttle as a child. He noticed that his vision in his right eye was gradually becoming worse.

His refraction, corrected with spectacles, was −4.25 −2.00 × 115 in his right eye and −5.50 −1.50 × 57 in his left eye, with a corrected distance visual acuity of 20/32 and 20/20, respectively. Because of allergies, the patient never tolerated contact lens wear for more than 2 hours.

On a slitlamp examination, we confirmed anterior subcapsular star-like cataract without any signs of zonulolysis. Optical biometry showed an axial length of 25.73 mm and 26.66 mm and an anterior chamber depth of 3.70 mm and 3.78 mm in the right and left eyes. Keratometric astigmatism measured by optical biometry was 1.56 diopters (D) at 30 degrees and 1.12 D at 138 degrees for the right and left eyes, and Scheimpflug tomography showed 1.1 D of regular astigmatism at 33 degrees in the right eye, and 0.9 D of regular astigmatism at 130 degrees in the left eye.

The patient is a professional photographer and asked for a treatment that would still allow him to be able to perform his job: he wants to read all the buttons on the camera up close and focus on the scenery in the distance.

What is your advice on this challenging case?
Impact of a Provider Tele-mentoring Learning Model on the Care of Medicaid-enrolled Patients With Diabetes
Authors: Cantor Joel C. , Chakravarty Sujoy , Farnham Jennifer , Nova Jose , Ahmad Sana , Flory James H.
Published: February 2022

Background:

Project ECHO (Extension for Community Healthcare Outcomes), a tele-mentoring program for health care providers, has been shown to improve provider-reported outcomes, but there is insufficient research on patient-level outcomes.

Objectives:

To evaluate the impact of primary care provider (PCP) participation in Project ECHO on the care of Medicaid enrollees with diabetes.

Research Design:

New Jersey Medicaid claims and encounter data and difference-in-differences models were used to compare utilization and spending between Medicaid patients seen by PCPs participating in a Project ECHO program to those of matched nonparticipating PCPs.

Subjects:

A total of 1776 adult Medicaid beneficiaries (318 with diabetes), attributed to 25 participating PCPs; and 9126 total (1454 diabetic) beneficiaries attributed to 119 nonparticipating PCPs.

Measures:

Utilization and spending for total inpatient, diabetes-related inpatient, emergency department, primary care, and endocrinologist services; utilization of hemoglobin A1c tests, eye exams, and diabetes prescription medications among diabetics, and total Medicaid spending.

Results:

Participation in Project ECHO was associated with decreases of 44.3% in inpatient admissions (P=0.001) and 61.9% in inpatient spending (P=0.021) among treatment relative to comparison patients. Signs of most other outcome estimates were consistent with hypothesized program effects but without statistical significance. Sensitivity analyses largely confirmed these findings.

Conclusions:

We find evidence that Project ECHO participation was associated with large and statistically significant reductions of inpatient hospitalization and spending. The study was observational and limited by a small sample of participating PCPs. This study demonstrates the feasibility and potential value of quasi-experimental evaluation of Project ECHO patient outcomes using claims data.
Pediatric Neurogastroenterology and Motility Services in North America
Authors: Patel Dhiren , Safder Skaista S. , El‐Chammas Khalil , Kapavarapu Prasanna , Wheeler Justin , Mostamand Shikib , Khlevner Julie , Darbar Anil
Published: February 2022

To characterize the current availability and scope of pediatric neurogastroenterology and motility (PNGM) services in North America (NA), the NASPGHAN‐NGM committee distributed a self‐reporting survey through the NASPGHAN bulletin board and mailing listserv, to compile a list of NA centers offering PNGM services, PNGM training, and the types of diagnostic and therapeutic PNGM procedures and services. We received responses that 54 centers in NA offer some form of PNGM services. Previously, the NASPGHAN website had last updated information from 2015 listing 36 centers in the USA and 2 in Canada. The American Neurogastroenterology and Motility Society (ANMS) website had 16 PNGM centers listed in NA in 2021. Neither of these resources capture additional information regarding training, research, advanced diagnostics, and therapeutics, and all available PNGM services. Our data highlights the growth in the field of PNGM services, and the variability of their distribution throughout the continent.
Augmented Renal Clearance of Vancomycin in Suspected Sepsis: Single-Center, Retrospective Pediatric Cohort
Authors: Scully Peter Thomas , Lam Weng Man , Coronado Munoz Alvaro Jose , Modem Vinai Modini
Published: February 2022

OBJECTIVES:

To identify associations between augmented renal clearance (ARC) in pediatric patients treated for suspected sepsis and vancomycin pharmacokinetics. ARC has been associated with lower serum drug levels in both adult and pediatric cohorts for multiple drugs. We hypothesize that presence of ARC is associated with subtherapeutic initial vancomycin trough level (VTL).

DESIGN

Retrospective study, with patients divided into two groups based on the presence of ARC (estimated glomerular filtration rate [eGFR] above 130 mL/min/1.73 m2) in comparison with VTL. Multivariable logistic regression analysis was performed to evaluate the association between eGFR and subtherapeutic VTL.

SETTING:

Tertiary children’s hospital.

PATIENTS:

Hospitalized children (0–18 yr) initiated on empiric vancomycin therapy for suspected sepsis.

INTERVENTIONS:

Retrospective measurement of VTL, eGFR, and clinical variables.

MEASUREMENTS AND MAIN RESULTS:

Seventy-three patients were treated with empiric vancomycin for sepsis. ARC was present in 32 patients (44%). Subtherapeutic first VTL was present in 40 patients (55%). Higher eGFR was independently associated with subtherapeutic VTL in the multivariable logistic regression analysis.

CONCLUSIONS:

Subtherapeutic VTL is associated with ARC in our single-center retrospective cohort of children with suspected sepsis. This problem may present a potential risk of treatment failure in Gram-positive sepsis or longer time to clinical response. Prospective studies to investigate the clinical significance and effect of optimizing vancomycin dose in patients with ARC are recommended.
Current Medication Practices and Preferences Among Patients With Psoriatic Arthritis
Authors: Schwartzman Monica , Abutalib Zafir , Mandl Lisa A.
Published: February 2022

Objective

The aim of this study was to evaluate real-world psoriatic arthritis (PsA) medication use and patient medication preferences.

Methods

This is a cross-sectional survey of Classification for Psoriatic Arthritis criteria defined PsA patients recruited from a single-center PsA registry from June to September 2020. Preferences were ranked on a 5-point Likert scale ranging from “not at all important” to “extremely important.”

Results

One hundred thirty-seven patients (29%) responded. The median duration (years) of PsA skin and joint symptoms was 19 (interquartile range, 10–34) and 12 (interquartile range, 8–21), respectively. The most common initial immunomodulatory medications were anti–tumor necrosis factor α (35%), methotrexate (19%), and anti–phosphodiesterase 4 (anti-PDE4) (12.4%). At survey administration, the most common immunomodulatory therapies were anti–tumor necrosis factor α (30%), anti–interleukin 17 (IL-17) (20.4%), and methotrexate (10.2%). After 2018, when updated guidelines from the American College of Rheumatology/National Psoriasis Foundation were published, a significantly higher percentage of patients' first medication was an anti–IL-17 compared with 2018 or earlier (30% vs 3.5%, p < 0.001), a pattern also seen with anti-PDE4 (40% vs 11.5%, p < 0.012). Medication preferences most ranked as “extremely” important were prevention of joint damage (80%), ability to perform daily activities (71%), prevention of pain (70.1%), rheumatologist recommendation (63%), and medication adverse effects (62%).

Conclusions

The significant increase of anti–IL-17 and anti-PDE4 medications as initial treatment after 2018 may reflect their inclusion as potential initial therapy in updated guidelines, along with the importance placed by patients on medication adverse effects. Given the expanding armamentarium of PsA medications, it is increasingly important to align patient preferences and therapeutic options to ensure durable use of effective therapy.