bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoselective sharp enucleation of the prostate with a front-firing 532-nm laser versus photoselective vaporization of the prostate in the treatment of benign prostatic hyperplasia: a randomised controlled trial with 1-year followup results
Authors: Liu Zhengchao , Chen Zhipeng , Yan Dishi , Jiang Tao , Fu Jian , Zheng Jun , Zhou Yuanxiu , Zhou Zhansong , Shen Wenhao
Published: November 2022

Background

We designed a new surgical procedure to treat benign prostatic hyperplasia(BPH). In order to verify its effectiveness and safety, we constructed this randomized controlled trial to compare the efficacy of our innovative enucleation technique- photoselective sharp enucleation of the prostate (PSEP), with a front-firing 532-nm laser and the traditional technique-photoselective vaporization of the prostate (PVP) in the treatment of BPH.

Methods

A total of 154 consecutive patients diagnosed with bladder outlet obstruction secondary to BPH in our center from June 2018 to April 2019 were randomly divided into the PSEP group (n = 77) and the PVP group (n = 77) and were treated surgically with either PSEP or PVP. All patients were assessed preoperatively and followed up at 1, 6, and 12 months postoperatively. The international prostate symptom score,quality-of-life score, postvoid residual urine volume, maximum urine flow rate, prostate volume, prostate-specific antigen, and adverse events were compared.

Results

The lower urinary tract symptoms in both groups were significantly improved compared with the baseline at 1, 6, and 12 months postoperatively. The PSEP and PVP groups had an equivalent International Prostate Symptom Score, quality-of-life score, postvoid residual urine volume, maximum urine flow rate, prostate-specific antigen at each follow-up (P > 0.05). The median operative time in the PSEP group was significantly shorter than that in the PVP group (35 min vs. 47 min, P < 0.001). At 6 and 12 months after surgery, the median PV in the PSEP group was smaller than that in the PVP group (P < 0.05). Complication rates were comparable between the groups.

Conclusion

Both PSEP and PVP can achieve good efficacy and safety in the treatment of BPH. PSEP can remove more tissue than PVP and is associated with higher efficiency. In addition, PSEP eliminates the problem of lack of tissue samples associated with PVP.

Trial registration

Chinese Clinical Trial Registry, identifie:ChiCTR1800015867, date:25/04/2018.
Gonadotropin-releasing hormone agonist for the preservation of ovarian function in survivors of haematopoietic stem cell transplantation for haematological diseases
Authors: Wang Zhenhong , An Jian , Wang Chaohua
Published: November 2022

Objective

Administration of GnRH agonist (GnRHa) prior to chemotherapy may decreases the risk of gonadal dysfunction in patients with tumors. However, relevant data in haematopoietic stem cell transplantation (HSCT) recipients has not yet been established. Hence, the present study was designed to evaluate the clinical efficacy of GnRHa cotreatment prior to myeloablative regimens on ovarian protection in female survivors of HSCT for haematological diseases.

Patients and methods

Eligible patients were divided into a GnRHa group and a control group. Medical records regarding age at HSCT; diagnosis/indication for HSCT; pre- and posttransplantation serum sex hormone levels; menstruation and perimenopausal symptoms after HSCT were collected and compared. The primary and secondary outcome was the incidence of premature ovarian insufficiency (POI) symptoms associated with hypoestrogenism.

Results

A total of 330 patients were enrolled in the study: 19 patients were lost to follow-up, and clinical information was obtained in 311 patients. There was no significant difference in the primary outcome of follow-up between the two groups (78.50% [84 of 107] for the GnRHa group versus 83.33% [170 of 204] for the control group). The adjusted relative risks (RR) and 95% confidence interval (CI) were 1.19 and 0.73–1.93 (P = 0.487). Among patients who received cotreatment with GnRHa, 62.62% (67 of 107) complained of perimenopausal symptoms, which was significantly lower than the 74.51% (152 of 204) in the control group (adjusted RR: 1.46, 95% CI: 1.04–2.06, P = 0.031).

Conclusion

GnRHa cotreatment may not decrease the POI rate in HSCT survivors. However, it may reduce perimenopausal symptoms in this population, suggesting a potential benefit of GnRHa in clinical practice and warrant further researches.
Prediction of amyloid PET positivity via machine learning algorithms trained with EDTA-based blood amyloid-β oligomerization data
Authors: Youn Young Chul , Kim Hye Ryoun , Shin Hae-Won , Jeong Hae-Bong , Han Sang-Won , Pyun Jung-Min , Ryoo Nayoung , Park Young Ho , Kim SangYun
Published: November 2022

Background

The tendency of amyloid-β to form oligomers in the blood as measured with Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) is a valuable biomarker for Alzheimer’s disease and has been verified with heparin-based plasma. The objective of this study was to evaluate the performance of ethylenediaminetetraacetic acid (EDTA)-based MDS-OAβ and to develop machine learning algorithms to predict amyloid positron emission tomography (PET) positivity.

Methods

The performance of EDTA-based MDS-OAβ in predicting PET positivity was evaluated in 312 individuals with various machine learning models. The models with various combinations of features (i.e., MDS-OAβ level, age, apolipoprotein E4 alleles, and Mini-Mental Status Examination [MMSE] score) were tested 50 times on each dataset.

Results

The random forest model best-predicted amyloid PET positivity based on MDS-OAβ combined with other features with an accuracy of 77.14 ± 4.21% and an F1 of 85.44 ± 3.10%. The order of significance of predictive features was MDS-OAβ, MMSE, Age, and APOE. The Support Vector Machine using the MDS-OAβ value only showed an accuracy of 71.09 ± 3.27% and F−1 value of 80.18 ± 2.70%.

Conclusions

The Random Forest model using EDTA-based MDS-OAβ combined with the MMSE and apolipoprotein E status can be used to prescreen for amyloid PET positivity.
Custom gene expression panel for evaluation of potential molecular markers in hepatocellular carcinoma
Authors: Pallerla Srinivas Reddy , Hoan Nghiem Xuan , Rachakonda Sivaramakrishna , Meyer Christian G. , Van Tong Hoang , Toan Nguyen Linh , Linh Le Thi Kieu , Giang Dao Phuong , Kremsner Peter G. , Bang Mai Hong , Song Le Huu , Velavan Thirumalaisamy P.
Published: November 2022

Background

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. It is a highly heterogeneous disease with poor prognosis and limited treatment options, which highlights the need for reliable biomarkers. This study aims to explore molecular markers that allow stratification of HCC and may lead to better prognosis and treatment prediction.

Materials and methods

We studied 20 candidate genes (HCC hub genes, potential drug target genes, predominant somatic mutant genes) retrieved from literature and public databases with potential to be used as the molecular markers. We analysed expression of the genes by RT-qPCR in 30 HCC tumour and adjacent non-tumour paired samples from Vietnamese patients. Fold changes in expression were then determined using the 2−∆∆CT method, and unsupervised hierarchical clustering was generated using Cluster v3.0 software.

Results

Clustering of expression data revealed two subtypes of tumours (proliferative and normal-like) and four clusters for genes. The expression profiles of the genes TOP2A, CDK1, BIRC5, GPC3, IGF2, and AFP were strongly correlated. Proliferative tumours were characterized by high expression of the c-MET, ARID1A, CTNNB1, RAF1, LGR5, and GLUL1 genes. TOP2A, CDK1, and BIRC5 HCC hub genes were highly expressed (> twofold) in 90% (27/30), 83% (25/30), and 83% (24/30) in the tissue samples, respectively. Among the drug target genes, high expression was observed in the GPC3, IGF2 and c-MET genes in 77% (23/30), 63% (19/30), and 37% (11/30), respectively. The somatic mutant Wnt/ß-catenin genes (CTNNB1, GLUL and LGR5) and TERT were highly expressed in 40% and 33% of HCCs, respectively. Among the HCC marker genes, a higher percentage of tumours showed GPC3 expression compared to AFP expression [73% (23/30) vs. 43% (13/30)].

Conclusion

The custom panel and molecular markers from this study may be useful for diagnosis, prognosis, biomarker-guided clinical trial design, and prediction of treatment outcomes.
Randomized, double-blind, placebo-controlled, crossover trial of oral doxycycline for epistaxis in hereditary hemorrhagic telangiectasia
Authors: Thompson K. P. , Sykes J. , Chandakkar P. , Marambaud P. , Vozoris N. T. , Marchuk D. A. , Faughnan M. E.
Published: November 2022

Background

Vascular malformations in hereditary hemorrhagic telangiectasia (HHT) lead to chronic recurrent bleeding, hemorrhage, stroke, heart failure, and liver disease. There is great interest in identifying novel therapies for epistaxis in HHT given its associated morbidity and impact on quality of life. We aimed to measure the effectiveness of oral doxycycline for the treatment of epistaxis and explore mechanisms of action on angiogenic, inflammatory and pathway markers in HHT using a randomized controlled trial.

Methods

13 HHT patients with epistaxis were recruited from the Toronto HHT Center at St. Michael’s Hospital. Recruitment was stopped early due to COVID-19-related limitations. The study duration was 24 months. Patients were randomly assigned to the treatment-first or placebo-first study arm. We compared the change in weekly epistaxis duration and frequency, biomarkers, blood measurements, and intravenous iron infusion and blood transfusion requirements between treatment and placebo.

Results

There was no significant difference in the change in weekly epistaxis duration (p = 0.136) or frequency (p = 0.261) between treatment and placebo. There was no significant difference in the levels of MMP-9, VEGF, ANG-2, IL-6 or ENG with treatment. Hemoglobin levels were significantly higher (p = 0.0499) during treatment. Ferritin levels were not significantly different between treatment and placebo. There was no significant difference in RBC transfusions between treatment periods (p = 0.299).

Conclusion

Overall, our study did not demonstrate effectiveness of doxycycline as a treatment for epistaxis in patients with HHT, though the study was underpowered. Secondary analyses provided new observations which may help guide future trials in HHT.

Trial Registration ClinicalTrials.gov, NCT03397004. Registered 11 January 2018 – Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03397004
Multimodal co-therapy for unaccompanied minors: a qualitative study
Authors: Guessoum Sélim Benjamin , Minassian Sevan , de Staël Pauline , Touhami Fatima , DiGiovanni Madeline , Radjack Rahmeth , Moro Marie Rose , Benoit Laelia
Published: November 2022

Background

Unaccompanied refugee minors—or unaccompanied minors—are children and adolescents who have been separated from parents and other relatives and are not being cared for by an adult. Unaccompanied minors are a vulnerable population, with numerous stressors and complex psychiatric symptoms necessitating specialized mental health care. This study explores patients’ experiences of a Multimodal Co-Therapy for Unaccompanied Minors (MUCTUM), which encompasses cultural, biological, narrative & institutional approaches to care.

Methods

MUCTUM is a co-therapy program for unaccompanied minors, with a psychiatrist, psychologist, native-language interpreter, and caseworker for each patient. In this qualitative study, we interviewed adolescents about their experiences with MUCTUM and analyzed these semi-structured interviews using a phenomenological framework (Interpretative Phenomenological Analysis).

Results

Qualitative analysis of 16 interviews discovered that unaccompanied minors felt misunderstood before participating in MUCTUM, describing a sense of strangeness and loneliness in relation to psychiatric symptoms. Several youths experienced triple stigmatization: of being unaccompanied minors, of suffering from psychotrauma, and of being mental health patients. We further describe three overarching domains that inform on MUCTUM support to unaccompanied minors: (1) A safe space for unaccompanied minors; (2) Helpful interventions during therapy; and (3) Narrating one’s story can “set us free” if guided carefully by care providers.

Conclusion

This study suggests that MUCTUM therapy may efficiently support unaccompanied minors’ mental health by acknowledging their hierarchy of needs. Psychotherapeutic strategies include creating a safe place, providing culturally appropriate care and patient-centered therapy, addressing concrete problems, supporting relationships, and making use of limited reparenting in therapy. Delayed and progressive inquiry about traumatic events may be beneficial. Replication of these findings and their field application is warranted.
Comparison of intestinal flora between patients with chronic and advanced Schistosoma japonicum infection
Authors: Zhou Chen , Li Junhui , Guo Chen , Zhou Zhaoqin , Yang Zhen , Zhang Yu , Jiang Jie , Cai Yu , Zhou Jie , Ming Yingzi
Published: November 2022

Background

Schistosoma japonicum infection is an important public health problem, imposing heavy social and economic burdens in 78 countries worldwide. However, the mechanism of transition from chronic to advanced S. japonicum infection remains largely unknown. Evidences suggested that gut microbiota plays a role in the pathogenesis of S. japonicum infection. However, the composition of the gut microbiota in patients with chronic and advanced S. japonicum infection is not well defined. In this study, we compared the composition of the intestinal flora in patients with chronic and advanced S. japonicum infection.

Methods

The feces of 24 patients with chronic S. japonicum infection and five patients with advanced S. japonicum infection from the same area were collected according to standard procedures, and 16S rRNA sequencing technology was used to analyze the intestinal microbial composition of the two groups of patients.

Results

We found that alteration occurs in the gut microbiota between the groups of patients with chronic and advanced S. japonicum infections. Analysis of alpha and beta diversity indicated that the diversity and abundance of intestinal flora in patients with advanced S. japonicum infection were lower than those in patients with chronic S. japonicum infection. Furthermore, Prevotella 9, Subdoligranulum, Ruminococcus torques, Megamonas and Fusicatenibacter seemed to have potential to discriminate different stages of S. japonicum infection and to act as biomarkers for diagnosis. Function prediction analysis revealed that microbiota function in the chronic group was focused on translation and cell growth and death, while that in the advanced group was concentrated on elevating metabolism-related functions.

Conclusions

Our study demonstrated that alteration in gut microbiota in different stages of S. japonicum infection plays a potential role in the pathogenesis of transition from chronic to advanced S. japonicum infection. However, further validation in the clinic is needed, and the underlying mechanism requires further study.
Network reconstruction for trans acting genetic loci using multi-omics data and prior information
Authors: Hawe Johann S. , Saha Ashis , Waldenberger Melanie , Kunze Sonja , Wahl Simone , Müller-Nurasyid Martina , Prokisch Holger , Grallert Harald , Herder Christian , Peters Annette , Strauch Konstantin , Theis Fabian J. , Gieger Christian , Chambers John , Battle Alexis , Heinig Matthias
Published: November 2022

Background

Molecular measurements of the genome, the transcriptome, and the epigenome, often termed multi-omics data, provide an in-depth view on biological systems and their integration is crucial for gaining insights in complex regulatory processes. These data can be used to explain disease related genetic variants by linking them to intermediate molecular traits (quantitative trait loci, QTL). Molecular networks regulating cellular processes leave footprints in QTL results as so-called trans-QTL hotspots. Reconstructing these networks is a complex endeavor and use of biological prior information can improve network inference. However, previous efforts were limited in the types of priors used or have only been applied to model systems. In this study, we reconstruct the regulatory networks underlying trans-QTL hotspots using human cohort data and data-driven prior information.

Methods

We devised a new strategy to integrate QTL with human population scale multi-omics data. State-of-the art network inference methods including BDgraph and glasso were applied to these data. Comprehensive prior information to guide network inference was manually curated from large-scale biological databases. The inference approach was extensively benchmarked using simulated data and cross-cohort replication analyses. Best performing methods were subsequently applied to real-world human cohort data.

Results

Our benchmarks showed that prior-based strategies outperform methods without prior information in simulated data and show better replication across datasets. Application of our approach to human cohort data highlighted two novel regulatory networks related to schizophrenia and lean body mass for which we generated novel functional hypotheses.

Conclusions

We demonstrate that existing biological knowledge can improve the integrative analysis of networks underlying trans associations and generate novel hypotheses about regulatory mechanisms.
Fungal esophagitis associated with tuberculous pericarditis in an human immunodeficiency virus-positive patient: a case report
Authors: Silva Gleiciere Maia , de Sousa Bruna Rodrigues , Torres Kaliny Benicio , Neves Rejane Pereira , de Melo Heloisa Ramos Lacerda , de Lima-Neto Reginaldo Gonçalves
Published: November 2022

Background

Opportunistic infections are frequent in people living with the human immunodeficiency virus who either do not have access to antiretroviral therapy (ART) or use it irregularly. Tuberculosis is the most frequent infectious disease in PLHIV and can predispose patients to severe fungal infections with dire consequences.

Case presentation

We describe the case of a 35-year-old Brazilian man living with human immunodeficiency virus (HIV) for 10 years. He reported no adherence to ART and a history of histoplasmosis with hospitalization for 1 month in a public hospital in Natal, Brazil. The diagnosis was disseminated Mycobacterium tuberculosis infection. He was transferred to the health service in Recife, Brazil, with a worsening condition characterized by daily fevers, dyspnea, pain in the upper and lower limbs, cough, dysphagia, and painful oral lesions suggestive of candidiasis. Lymphocytopenia and high viral loads were found. After screening for infections, the patient was diagnosed with tuberculous pericarditis and esophageal candidiasis caused by Candida tropicalis. The isolated yeasts were identified using the VITEK 2 automated system and matrix-assisted laser desorption/ionization time-of-flight–mass spectrometry. Antifungal microdilution broth tests showed sensitivity to fluconazole, voriconazole, anidulafungin, caspofungin, micafungin, and amphotericin B, with resistance to fluconazole and voriconazole. The patient was treated with COXCIP-4 and amphotericin deoxycholate. At 12 days after admission, the patient developed sepsis of a pulmonary focus with worsening of his respiratory status. Combined therapy with meropenem, vancomycin, and itraconazole was started, with fever recurrence, and he changed to ART and tuberculostatic therapy. The patient remained clinically stable and was discharged with clinical improvement after 30 days of hospitalization.

Conclusion

Fungal infections should be considered in patients with acquired immunodeficiency syndrome as they contribute to worsening health status. When mycoses are diagnosed early and treated with the appropriate drugs, favorable therapeutic outcomes can be achieved.
Characteristics of GGBFS-Based Pervious Concrete Considering Rheological Properties of the Binder
Authors: Oinam Yanchen , Ju Suhawn , Gwon Seongwoo , Shin Myoungsu , Pyo Sukhoon
Published: November 2022

To mitigate environmental challenges, such as urban flooding, noise pollution, and the urban heat island effect, pervious concrete has been developed. This research was intended to develop pervious concrete made from ground granulated blast furnace slag (GGBFS) to further decrease the environmental impact of the construction sector by reducing the content of ordinary Portland cement (OPC). The primary objective of the mix proportion was to maximize water permeability while meeting the required compressive strength. Two levels (60 and 100%) of OPC replacement by GGBFS were evaluated and compared to OPC-only concrete, and two target porosities (10 and 15%) were achieved by modifying the binder-to-aggregate ratio. CaO and CaCl2 were utilized as an activator and an accelerator, respectively, for the GGBFS only binder. Characteristics of the pervious concrete were determined with the compressive strength, porosity and water permeability test. Meanwhile, the effects of the rheological properties of binders on the water permeability and compressive strength of pervious concretes was evaluated. According to the results, the permeability of pervious concretes always exhibited a positive correlation with porosity, regardless of binder type. Although, the pervious concrete made with CaO-activated GGBFS has a lower compressive strength than the other two cases (60% GGBFS and only OPC), it still meets the minimum strength requirement. Based on the rheology studies of binder, it was found that, the adhesion force of the binder and the compressive strength of the pervious concrete decreases, as evaluated by rheology studies on binders. The CT scan revealed that when the adhesive force of the binder was weaker, the local porosity was higher (i.e., pore volume was larger) at the bottom of the specimen, which might be due to the limited consolidation and compaction of the binder between aggregate particles at the bottom due to its higher plastic viscosity.
Revisiting the multidimensional interaction model of stress, anxiety and coping during the COVID-19 pandemic: a longitudinal study
Authors: Rogowska Aleksandra M. , Ochnik Dominika , Kuśnierz Cezary
Published: November 2022

Background

Although the Multidimensional Interaction Model of Stress, Anxiety and Coping (MIMSAC) has been known for years, there is a lack of research examining this theory longitudinally in stressful events. This study aims to revisit the MIMSAC among university students during the COVID-19 pandemic.

Methods

A prospective cohort study with the longitudinal design was performed during the first (W1, March 30–April 29, 2020) and second wave (W2, November 3–December 3, 2020) of the COVID-19 pandemic. A total of 216 university students with a mean age of 22 years (ranging from 20 to 36, M = 22.13, SD = 2.04) participated in the study. An online survey included Perceived Stress Scale, Coping Inventory for Stressful Situations, and Generalized Anxiety Disorder.

Results

Due to the MIMSAC, all variables changed substantially across W1 and W2, adapting to an unpredictable environment. Women scored higher than men in stress, anxiety, emotion- and avoidance-oriented coping styles. We found the indirect effect of emotion-oriented coping on the stress-anxiety relationship and task-oriented coping on the anxiety-stress interaction. Avoidance was not found as a mediator in the stress-anxiety interaction.

Conclusion

Emotion-oriented coping adversely affected mental health, increasing anxiety in response to stress during the COVID-19 pandemic. Task-oriented coping efficiently decreased stress in reaction to high anxiety, but only in men. Avoidance seems to be an ineffective coping style during the COVID-19 pandemic. Campus intervention programs should focus on reducing negative emotions and increasing the frequency of task-oriented coping strategies among university students.
The flipped house and the bubble. Domestic space in the time of coronavirus
Authors: Spanedda Francesco , Fusaro Matteo Carmine
Published: November 2022

The SARS-CoV-2 pandemic put the spatial layouts of contemporary housing to the test. During the strict lockdowns in the early phases of the outbreak and the limited, temporary restrictions of the later phases, the safeguarding of public health was inevitably enforced by confining people at home, thus severing, by reasons of force majeure, the traditional relationship between the house and the city. As a result, every household had to contain within itself all aspects of public and private life, regardless of the spatial qualities and the extension of the dwelling. The unexpected new role of the last defence line against the virus showed all the advantages and limits of contemporary housing and the need for a rethinking of some of their typical features. The aim of this article is to investigate how the residential space, as a whole and in its constituent parts, has become a fundamental element in a difficult period, managing to incorporate unexpected functions and requirements but also revealing a series of congenital weaknesses.
Linking migration and microbiota at a major stopover site in a long-distance avian migrant
Authors: Thie Nikki , Corl Ammon , Turjeman Sondra , Efrat Ron , Kamath Pauline L. , Getz Wayne M. , Bowie Rauri C. K. , Nathan Ran
Published: November 2022

Migration is one of the most physical and energetically demanding periods in an individual bird’s life. The composition of the bird’s gut or cloacal microbiota can temporarily change during migration, likely due to differences in diets, habitats and other environmental conditions experienced en route. However, how physiological condition, migratory patterns, and other drivers interact to affect microbiota composition of migratory birds is still unclear. We sampled the cloacal bacterial microbiota of a long-distance migrant, the steppe buzzard (Buteo buteo vulpinus), at an important spring stopover bottleneck in Eilat, Israel, after crossing the ca. 1800 km Sahara Desert. We examined whether diversity and composition of the cloacal microbiota varied with body condition, sex, movement patterns (i.e., arrival time and migration distance), and survival. Early arrival to Eilat was associated with better body condition, longer post-Eilat spring migration distance, higher microbial α-diversity, and differences in microbiota composition. Specifically, early arrivals had higher abundance of the phylum Synergistota and five genera, including Jonquetella and Peptococcus, whereas the phylum Proteobacteria and genus Escherichia-Shigella (as well as three other genera) were more abundant in later arrivals. While the differences in α-diversity and Escherichia-Shigella seem to be mainly driven by body condition, other compositional differences associated with arrival date could be indicators of longer migratory journeys (e.g., pre-fueling at wintering grounds or stopover habitats along the way) or migratory performance. No significant differences were found between the microbiota of surviving and non-surviving individuals. Overall, our results indicate that variation in steppe buzzard microbiota is linked to variation in migratory patterns (i.e., capture/arrival date) and body condition, highlighting the importance of sampling the microbiota of GPS-tracked individuals on multiple occasions along their migration routes to gain a more detailed understanding of the links between migration, microbiota, and health in birds.
Predictability of lower incisor tip using clear aligner therapy
Authors: Smith Julia Meri , Weir Tony , Kaang Austin , Farella Mauro
Published: November 2022

Background

Uprighting incisors is particularly important with clear aligner therapy as incisor tip determines the mesio-distal space needed in the arch, and consequently the fit of the aligner. The objective of this study was to investigate the accuracy of ClinCheck® software to predict lower incisor tip by comparing digitally prescribed movements with actual clinical outcomes and to determine whether the presence of a vertically orientated rectangular composite attachment influences the efficacy of incisor tip.

Methodology

This retrospective study included 66 lower incisors from 42 non-extraction adult patients treated using the Invisalign® appliance. Twenty-one incisors had vertical attachments, while 45 incisors did not have any attachments. Lower incisor tip was measured at T0 (pre-treatment), T1 (predicted post-treatment) and T2 (achieved post-treatment) on digital models using metrology software. The change in position from T0 to T1 and T0 to T2 was measured from the estimated centre of resistance (CRes) of each tooth. The estimated centre of rotation was plotted relative to the CRes to describe the type of orthodontic tooth movement (OTM) predicted and achieved.

Results

Predicted incisor tip and achieved incisor tip were positively correlated (R2 = 0.55; p < 0.001). For every degree of tip planned 0.4 degrees of tip was achieved. The presence of an attachment resulted in 1.2 degrees greater tip (F = 3.7; p = 0.062) and 0.5 mm greater movement of the predicted apex of the tooth (F = 4.3; p = 0.042) compared with the no attachment group. The type of OTM achieved differed from the type predicted. Sixty-seven percent of incisors investigated were predicted to move by root movement, while 46% achieved this type of movement.

Conclusions

The amount of lower incisor tip achieved was on average substantially less than the ClinCheck® displayed. Vertically orientated rectangular attachments are recommended where large root movement is planned, and their presence slightly improves apex movement.
Pharmaceutical marketing: the example of drug samples
Authors: Alagha Emily Couvillon , Fugh-Berman Adriane
Published: November 2022

Branded drug samples are one of the most important promotional tools that pharmaceutical manufactures employ. Pharmaceutical sales representatives (“drug reps”) use samples to gain access to physicians and other prescribers. Sample provision is closely intertwined with visits by drug reps; detailing visits convince physicians to try new products, while sampling maintains the flow of prescriptions. Only drugs with the highest profit margins are sampled. Although physicians believe that samples save patients money, patients who receive samples have higher overall out-of-pocket costs. Most studies have found that patients in financial need are least likely to receive samples. Pharmaceutical marketers pitch samples as a low-risk way to deal with diagnostic uncertainty. In fact, there is no evidence that samples aid diagnosis. Sample availability may compromise patient safety by reducing compliance with guidelines and steering patients towards newer drugs, for which adverse effects have not been well-delineated. Although physicians believe that samples improve adherence for low-income patients, branded samples do not improve access or adherence Samples are not a charitable activity, but are instead a highly effective form of drug marketing. Sampling of branded drugs increase drug costs for everyone. Only a cohesive effort by clinicians, legislators and policymakers can end this practice. Evidence supports a ban on sample distribution of branded products.
Sporadic E layer characteristics at equatorial latitudes as observed by GNSS radio occultation measurements
Authors: Arras Christina , Resende Laysa Cristina Araújo , Kepkar Ankur , Senevirathna Gethmini , Wickert Jens
Published: November 2022

Scintillations in the signal-to-noise (SNR) profiles of GNSS radio occultation (RO) measurements at lower ionospheric altitudes are caused by compact layers of high ionization also known as sporadic E (Es) layers. It is widely accepted that Es layers are formed by the wind shear mechanism at northern and southern midlatitudes. However, approaching the equatorial regions, electric fields also control the formation and dispersal of these layers. In this paper we concentrate, in particular, on the occurrence rate and on the altitudes of Es layers appearing in a narrow band along the Earth’s magnetic equator. We analyzed several million of RO profiles concerning sporadic E occurrence as well as altitude and observed a high daily, seasonal and longitudinal variability which is controlled partly by zonal winds and electric fields. Especially Es layers at higher altitudes show a clear anticorrelation with the zonal electric field intensity measured by the Swarm satellites. Further, we solve the existing contradiction of Es layer signatures being present in equatorial ionosonde measurements while they are only rarely seen in RO recordings.

Graphical Abstract
Attenuation correction for PET/MRI to measure tracer activity surrounding total knee arthroplasty
Authors: Bourdon Caleigh E. , Koudys Zachary J. , Lanting Brent A. , Appleton C. Thomas , Thiessen Jonathan D. , Teeter Matthew G.
Published: November 2022

Background

Positron emission tomography (PET) in combination with magnetic resonance imaging (MRI) could allow inflammatory complications near total knee arthroplasty (TKA) to be studied early in their development. However, attenuation of the PET signal by the metal TKA implants imparts substantial error into measurements of tracer activity, and conventional MR-based attenuation correction (AC) methods have large signal voids in the vicinity of metal implants.

Purpose

To evaluate a segmentation-based AC approach to measure tracer uptake from PET/MRI scans near TKA implants.

Methods

A TKA implant (Triathlon, Stryker, Mahwah, USA) was implanted into a cadaver. Four vials were filled with [18F]fluorodeoxyglucose with known activity concentration (4.68 MBq total, 0.76 MBq/mL) and inserted into the knee. Images of the knee were acquired using a 3T PET/MRI system (Biograph mMR, Siemens Healthcare, Erlangen, Germany). Models of the implant components were registered to the MR data using rigid-body transformations and the other tissue classes were manually segmented. These segments were used to create the segmentation-based map and complete the AC. Percentage error of the resulting measured activities was calculated by comparing the measured and known amounts of activity in each vial.

Results

The original AC resulted in a percentage error of 64.1% from the known total activity. Errors in the individual vial activities ranged from 40.2 to 82.7%. Using the new segmentation-based AC, the percentage error of the total activity decreased to 3.55%. Errors in the individual vials were less than 15%.

Conclusions

The segmentation-based AC technique dramatically reduced the error in activity measurements that result from PET signal attenuation by the metal TKA implant. This approach may be useful to enhance the reliability of PET/MRI measurements for numerous applications.
In Multiple Myeloma, High-Risk Secondary Genetic Events Observed at Relapse Are Present From Diagnosis in Tiny, Undetectable Subclonal Populations
Authors: Lannes Romain , Samur Mehmet , Perrot Aurore , Mazzotti Celine , Divoux Marion , Cazaubiel Titouan , Leleu Xavier , Schavgoulidze Anaïs , Chretien Marie-Lorraine , Manier Salomon , Adiko Didier , Orsini-Piocelle Frederique , Lifermann François , Brechignac Sabine , Gastaud Lauris , Bouscary Didier , Macro Margaret , Cleynen Alice , Mohty Mohamad , Munshi Nikhil , Corre Jill , Avet-Loiseau Hervé
Published: November 2022

PURPOSE

Multiple myeloma (MM) is characterized by copy number abnormalities (CNAs), some of which influence patient outcomes and are sometimes observed only at relapse(s), suggesting their acquisition during tumor evolution. However, the presence of micro-subclones may be missed in bulk analyses. Here, we use single-cell genomics to determine how often these high-risk events are missed at diagnosis and selected at relapse.

MATERIALS AND METHODS

We analyzed 81 patients with plasma cell dyscrasias using single-cell CNA sequencing. Sixty-six patients were selected at diagnosis, nine at first relapse, and six in presymptomatic stages. A total of 956 newly diagnosed patients with MM and patients with first relapse MM have been identified retrospectively with required cytogenetic data to evaluate enrichment of CNA risk events and survival impact.

RESULTS

A total of 52,176 MM cells were analyzed. Seventy-four patients (91%) had 2-16 subclones. Among these patients, 28.7% had a subclone with high-risk features (del(17p), del(1p32), and 1q gain) at diagnosis. In a patient with a subclonal 1q gain at diagnosis, we analyzed the diagnosis, postinduction, and first relapse samples, which showed a rise of the high-risk 1q gain subclone (16%, 70%, and 92%, respectively). In our clinical database, we found that the 1q gain frequency increased from 30.2% at diagnosis to 43.6% at relapse (odds ratio, 1.78; 95% CI, 1.58 to 2.00). We subsequently performed survival analyses, which showed that the progression-free and overall survival curves were superimposable between patients who had the 1q gain from diagnosis and those who seemingly acquired it at relapse. This strongly suggests that many patients had 1q gains at diagnosis in microclones that were missed by bulk analyses.

CONCLUSION

These data suggest that identifying these scarce aggressive cells may necessitate more aggressive treatment as early as diagnosis to prevent them from becoming the dominant clone.
Gauge theory applied to magnetic lattices
Authors: Di Pietro A. , Ansalone P. , Basso V. , Magni A. , Durin G.
Published: November 2022

The generalizations of micromagnetic exchange including higher order interactions are normally performed phenomenologically. In this paper we combine graph and gauge field theory to provide a new procedure to perform the continuum limit of the Heisenberg model. Our approach allows to simultaneously account for the symmetries of the crystal, the effect of spin-orbit coupling and their interplay. We obtain a micromagnetic theory accounting for the crystal symmetry constraints at all orders in exchange. The form of the micromagnetic Dzyaloshinskii-Moriya interaction in all 32 point groups is calculated at the first order.
Predictors of Prescriber Preference for Expensive Insulins: A Single Institution Survey
Authors: Panjikaran Lloyd Devassy , Shee Vikram , Washington Terri
Published: November 2022

Background

The average cost of insulin has increased greatly recently, partly due to prescription of newer expensive insulins. This has caused insulin underuse among economically vulnerable uninsured patients. Herein, predictors of preference for expensive (higher retail price) insulins among primary care physicians are investigated.

Methods

Internal medicine and family medicine attending physicians and residents at West Suburban Medical Center (Oak Park, Illinois, USA) participated in a web-based survey (Qualtrics Survey Platform) via email between October 20, 2020, and November 10, 2020. Baseline characteristics, prescribing preferences (Insulins Ranks, lower rank indicates higher preference), factors determining insulin choice, pricing knowledge, dosing knowledge, and training were recorded. Insulins were classified as “Inexpensive” (retail price ≤ median insulin price) or “Expensive.” The mean rank of expensive and inexpensive insulins prescribed were calculated. Participants were divided into either the “Inexpensive Prescription Preferences” (IPP; mean rank of Inexpensive insulins ≤ mean rank of Expensive insulins) or “Expensive Prescription Preferences” (EPP) groups. Groups were compared. Multivariable logistic regression assessed predictors of IPP.

Results

The response rate was 78% (72/92). Among the 70 participants included, EPP (n = 43) and IPP participants (IPP, n = 27) had similar baseline characteristics (Physician Role, Specialty, and Practice Type), except EPP physicians graduated earlier (P = 0.011). EPP participants reported prescribing insulin glargine more often (P = 0.018) and also ranked it higher (P < 0.001). Logistic regression identified that previous Endocrine rotations (P = 0.031) and senior Physician Role (P = 0.001) predicted EPP.

Conclusion

Previous endocrinology rotations, and senior role predict prescription of insulins with a high retail price. Speculatively, training physicians in cheaper prescription practices may lower costs. Further studies are required to generalize these results.
The Effect of Night Float Rotation on Resident Sleep, Activity, and Well-Being
Authors: Ruan Alexandra , Klein Alexandra , Jhita Preya , Hasan-Hill Natalya , Shafer Steven L. , Flood Pamela D.
Published: November 2022

Background:

Night float call systems are becoming increasingly common at training programs with the goal of reducing fatigue related to sleep deprivation and sleep disturbance. Previous studies have shown that trainees obtain less sleep during the night float rotation and have decreased sleep efficiency for several days after the rotation. The impact on physical and emotional well-being has not been documented.

Methods:

Twenty-seven anesthesia residents were enrolled in a study using wearable sleep and activity trackers and National Institutes of Health Patient-Reported Outcome Measurement Information System (NIH PROMIS) surveys for sleep disturbance, fatigue, and positive affect to record data the week before (“baseline”), during (“night float”), and 1 week after (“recovery”) their night float rotation. Each subject’s data during the night float week and recovery week were compared to his or her own baseline week data using a paired, nonparametric analysis. The primary outcome variable was the change in average daily sleep hours during the night float week compared to the baseline week. Average daily rapid eye movement (REM) sleep, daily steps, and NIH PROMIS scores comparing night float and recovery weeks to baseline week were prespecified secondary outcomes. NIH PROMIS scores range from 0 to 100 with 50 as the national mean and more of the construct having a higher score.

Results:

There was no difference in average daily sleep hours between the night float and the baseline weeks (6.7 [5.9–7.8] vs 6.7 [5.5–7.7] hours, median [interquartile range]; P = .20). Residents had less REM sleep during the night float compared to the baseline weeks (1.1 [0.7–1.5] vs 1.4 [1.1–1.9] hours, P = .002). NIH PROMIS fatigue scores were higher during the night float than the baseline week (58.8 [54.6–65.1] vs 48.6 [46.0–55.1], P = .0004) and did not return to baseline during the recovery week (51.0 [48.6–58.8], P = .029 compared to baseline). Sleep disturbance was not different among the weeks. Positive affect was reduced after night float compared to baseline (39.6 [35.0–43.5] vs 44.8 [40.1–49.6], P = .0009), but returned to baseline during the recovery week (43.6 [39.6–48.2], P = .38).

Conclusions:

The residents slept the same number of total hours during their night float week but had less REM sleep, were more fatigued, and had less positive affect. All of these resolved to baseline except fatigue, that was still greater than the baseline week. This methodology appears to robustly capture psychophysiological data that might be useful for quality initiatives.
Metabolic rate and climate change across latitudes: evidence of mass-dependent responses in aquatic amphipods
Authors: Shokri Milad , Cozzoli Francesco , Vignes Fabio , Bertoli Marco , Pizzul Elisabetta , Basset Alberto
Published: November 2022

Predictions of individual responses to climate change are often based on the assumption that temperature affects the metabolism of individuals independently of their body mass. However, empirical evidence indicates that interactive effects exist. Here, we investigated the response of individual standard metabolic rate (SMR) to annual temperature range and forecasted temperature rises of 0.6–1.2°C above the current maxima, under the conservative climate change scenario IPCC RCP2.6. As a model organism, we used the amphipod Gammarus insensibilis, collected across latitudes along the western coast of the Adriatic Sea down to the southernmost limit of the species' distributional range, with individuals varying in body mass (0.4–13.57 mg). Overall, we found that the effect of temperature on SMR is mass dependent. Within the annual temperature range, the mass-specific SMR of small/young individuals increased with temperature at a greater rate (activation energy: E=0.48 eV) than large/old individuals (E=0.29 eV), with a higher metabolic level for high-latitude than low-latitude populations. However, under the forecasted climate conditions, the mass-specific SMR of large individuals responded differently across latitudes. Unlike the higher-latitude population, whose mass-specific SMR increased in response to the forecasted climate change across all size classes, in the lower-latitude populations, this increase was not seen in large individuals. The larger/older conspecifics at lower latitudes could therefore be the first to experience the negative impacts of warming on metabolism-related processes. Although the ecological collapse of such a basic trophic level (aquatic amphipods) owing to climate change would have profound consequences for population ecology, the risk is significantly mitigated by phenotypic and genotypic adaptation.
Head Pain in the Competitive Aquatic Athlete—An Approach to a Differential Diagnosis and Management
Authors: Beduhn Benjamin , Roe Garrett , Furst Wendy , Lewno Adam
Published: November 2022

Aquatic athletes not only face common headache etiologies similar to the general population and land-based athletes but also experience their own unique pathology. Posture, aquatic pressure, equipment, and even marine animals pose as unique causes to head pain in the aquatic athlete. Common head pain pathologies seen in the aquatic athlete include tension-type headaches, migraines, cluster headaches, and compressive headaches, including supraorbital neuralgia. Creating a thorough but focused differential diagnosis for head pain in the aquatic athlete can be a difficult and overwhelming task for some. We review both the common and not-so-common etiologies of head pain in the aquatic athlete and suggest a simple framework for assessment and treatment to diagnose and treat head pain in this specific population.
Fiscal Histories
Authors: Cochrane John H.
Published: November 2022

The fiscal theory states that inflation adjusts so that the real value of government debt equals the present value of real primary surpluses. Monetary policy remains important. The central bank can set an interest rate target, which determines the path of expected inflation, while news about the present value of surpluses drives unexpected inflation. I use fiscal theory to interpret historical episodes, including the rise and fall of inflation in the 1970s and 1980s, the long quiet zero bound of the 2010s, and the reemergence of inflation in 2021, as well as to analyze the gold standard, currency pegs, the ends of hyperinflations, currency crashes, and the success of inflation targets. Going forward, fiscal theory warns that inflation will have to be tamed by coordinated monetary and fiscal policy.
A Linear Panel Model with Heterogeneous Coefficients and Variation in Exposure
Authors: Sun Liyang , Shapiro Jesse M.
Published: November 2022

Linear panel models featuring unit and time fixed effects appear in many areas of empirical economics. An active literature studies the interpretation of the ordinary least squares estimator of the model, commonly called the two-way fixed effects (TWFE) estimator, in the presence of unmodeled coefficient heterogeneity. We illustrate some implications for the case where the research design takes advantage of variation across units (say, US states) in exposure to some treatment (say, a policy change). In this case, the TWFE can fail to estimate the average (or even a weighted average) of the units’ coefficients. Under some conditions, there exists no estimator that is guaranteed to estimate even a weighted average. Building on the literature, we note that when there is a unit totally unaffected by treatment, it is possible to estimate an average effect by replacing the TWFE with an average of difference-in-differences estimators.