bluuebunny/crossref_metadata_2025 huggingface dataset:
The comparisons of different therapeutic modalities for idiopathic achalasia
Authors: Shiu Sz-Iuan , Chang Chung-Hsin , Tu Yu-Kang , Ko Chung-Wang
Published: June 2022

Background

: Current guidelines recommend per-oral endoscopic myotomy (POEM) and laparoscopic Heller's myotomy (LHM) as first-line treatment of idiopathic achalasia, but the optimum choice between different endoscopic and surgical modalities remains inconclusive. We conducted a network meta-analysis to compare the efficacy of 8 treatments for idiopathic achalasia.

Materials and methods

: Three major bibliographic databases were reviewed for enrollment of randomized controlled trials between January 2000 and June 2021. We included adults with idiopathic achalasia and compared two or more of eight interventions including botulinum toxin injection (BTI), pneumatic dilation (PD), BTI + PD, LHM without fundoplication, LHM followed with Dor or Toupet fundoplication, and POEM using either the anterior or posterior approach. Our focus was on clinical success rate, postsurgical acid reflux, and moderate-to-severe adverse events.

Results

: Twenty-four studies involved a total of 1987 participants for analysis. When compared with PD, POEM with anterior approach, POEM with posterior approach, LHM + Toupet, and LHM + Dor were all significantly superior to the other regimens in short-term efficacy, with POEM with anterior approach and LHM + Dor showing better improvement in mid-term efficacy. BTI showed a significantly lower efficacy than PD in both periods. Regarding safety, only LHM without fundoplication was significantly associated with higher acid reflux than PD, while LHM + Toupet, LHM without fundoplication, and LHM + Dor showed a non-significant increase in moderate-to-severe adverse events.

Conclusions

: For idiopathic achalasia, we suggest that POEM with an anterior or posterior approach and LHM with Dor or Toupet fundoplication be initially recommended. On the contrary, both LHM without fundoplication and BTI are not recommended as definitive therapy.
Acute kidney injury due to direct infiltration by lymphoplasmacytic lymphoma secreting IgG paraproteins
Authors: Kim Seongmin , Bae Wooram , Choi Jungyoon , Lee Tae Won , Song Dae Hyun , Bae Eunjin , Jang Ha Nee , Chang Se-Ho , Park Dong Jun
Published: June 2022

Introduction:

Waldenström's macroglobulinemia is a lymphoplasmacytic lymphoma (LPL) associated with a monoclonal immunoglobulin M protein. Although acute kidney injury (AKI) due to immunoglobulin M paraprotein infiltration into the renal interstitium has been reported, there has been no report of AKI with invasion of the immunoglobulin G paraprotein into the renal interstitium in a patient with LPL.

Patient concerns:

A 65-year-old male was admitted to our hospital with fatigue and decreased renal function. He complained of a 3-kg weight loss in the last 3 months.

Diagnosis:

The initial blood urea nitrogen and serum creatinine levels were 55.9 and 1.83 mg/dL, respectively. Serum protein electrophoresis revealed a monoclonal component (3.5 g/dL) in the gamma region and immunofixation electrophoresis showed an immunoglobulin G kappa monoclonal protein. Renal pathology revealed that CD3–CD20+ CD138+ lymphoid cells had infiltrated the renal interstitium. A bone marrow biopsy was compatible with LPL.

Interventions:

Intravenous methylprednisolone (1 mg/kg) was administered after confirming the renal pathological findings.

Outcomes:

Serum creatinine decreased to 0.8 mg/dL 14 days after treatment

Conclusions:

Physicians should recognize LPL secreting various immunoglobulins as a possible cause of AKI when renal failure of unknown etiology and serum immunoglobulin paraprotein is present. A kidney biopsy should be performed for definitive diagnosis and appropriate management.
An apparent primitive mass of the mesentery
Authors: Costanzo Antonio , Canziani Marco , Ferrari Cesare Carlo , Bertocchi Valentina , Cutaia Saro , Bucci Eraldo Oreste , Uslenghi Elisabetta , Ferretti Andrea , De Luca Marco , Ceriani Fabio
Published: June 2022

Introduction:

Neuroendocrine tumours (NETs) are rare tumors. 55% of NETs originate in the gastrointestinal tract and the liver is the most common site of distant metastases. Serum chromogranin A is the most common biomarker for assessing the extent of disease and monitoring treatment; carcinoid syndrome occurs in 19% of NETs and is characterized by chronic diarrhea or flushing. Primary mesenteric NETs are rare and have been described only in case reports in literature; our case is an apparent primary mesenteric NETs with a surgical program to remove the mesenteric mass and subrenal interaortocaval and retrocaval lymphadenectomies.

Patient concerns:

A 73-year old man came to us because he had been experiencing abdominal pain for a year and he had recently developed diabetes mellitus. He was an active smoker with arterial hypertension.

Diagnosis:

After a computed tomography scan and 68 Gallium-positron emission tomography, a diagnosis of what appeared to be a primary mesenteric NET with retrocaval and interaortocaval lymph nodes was made. Laparoscopic biopsy showed NET G2 positive for serotonin, chromogranin A, synaptophysin.

Interventions:

The intraoperative finding of a primitive ileum-NET changed the surgical program. We removed the mesenteric mass with the lymph nodes of the superior mesenteric vessel and the middle distal ileum along with the cecum.

Outcomes:

The postoperative course was normal, and the patient was discharged on the seventh postoperative day without signs of short bowel syndrome. Follow-up at 6 months revealed no evidence of short bowel syndrome or disease progression.

Conclusion:

68 Gallium-positron emission tomography does not show NETs smaller than 0.5 mm. Accurate palpation of the intestine is essential during surgery for NETs for two reasons: to find the primitive, and because of the risk of multiple intestinal primitives.
Ceftazidime-avibactam and intrapleural amikacin therapy for extensively drug-resistant Pseudomonas aeruginosa thoracic empyema
Authors: Chen Tzu-Ting , Chen Shu-Mei , Liu Hsin-Yi
Published: June 2022

Introduction:

Thoracic empyema and concomitant bronchopleural fistula are serious complications of pneumonia. The treatment of empyema caused by extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has become increasingly challenging.

Patient's concerns and important clinical findings:

A 57-year-old woman with controlled schizophrenia developed hospital-associated bacterial pneumonia secondary to P. aeruginosa on day 13 of hospitalization for brain meningioma surgery.

Diagnosis:

Chest radiography and computed tomography revealed right-sided necrotizing pneumonia with pneumothorax, a focal soft tissue defect over the right lower chest wall, and a mild right-sided encapsulated pleural effusion with consolidation. XDR-PA was isolated on empyema cultures.

Interventions:

The patient was treated with intrapleural amikacin as a bridge to video-assisted thoracoscopic surgery, followed by novel ceftazidime-avibactam therapy.

Outcomes:

On the 104th day of admission, the patient underwent chest wall debridement and closure. The patient was discharged on day 111. Twenty-eight days after discharge, there were no observable sequelae of empyema.

Conclusion:

Although the minimum inhibitory concentration of ceftazidime-avibactam for XDR-PA is relatively high (8 mg/L), this report emphasizes the efficacy of ceftazidime-avibactam treatment for XDR-PA empyema, as well as the importance of source control.
Intercalary staphyloma after strabismus surgery in a patient with Marfan syndrome
Authors: Kim Ju Mi , Kim Jae-young , Sung Jae-yeon , Hwang Jae Yul , Lee Yeon-Hee
Published: June 2022

Rationale:

A few cases of intercalary staphyloma have been reported in patients with Marfan syndrome, but we believe that this is the first case of intercalary staphyloma in Marfan syndrome developing after strabismus surgery.

Patient concerns:

A 9-year-old girl diagnosed with Marfan syndrome visited a strabismus clinic for treatment of esotropia. Both eyes were aphakic and had 60 prism diopter esotropia at distance and 55 prism diopter esotropia at near. There were no corneal, conjunctival, or scleral abnormalities. Six millimeters of recession was performed on both medial rectus muscles via an inferonasal fornix approach under general anesthesia. 5 days after surgery, a dark gray protruding lesion was observed on the upper nasal side of the left eye.

Diagnoses:

Intraocular ultrasonography showed no bleeding, retinal detachment, or other abnormal findings. Computed tomography showed a conical protrusion of the scleral wall which was diagnosed as intercalary staphyloma.

Interventions:

To reduce risk of progression of the staphyloma in the left eye and to reduce risk of development of a new staphyloma, intraocular pressure lowering eye drops were administered.

Outcomes:

We just observed it without any intervention except the intraocular pressures lowering eye drops. It remained stable for 12 months.

Lessons:

Clinicians need to be alert to the possibility of this serious complication in Marfan syndrome patients after minor surgical trauma, which can occur during uneventful strabismus surgery.
Volumetric computed tomography analysis for gastroduodenal and pancreaticoduodenal artery aneurysm formation
Authors: Maeno Ryohei , Hoshina Katsuyuki , Miyahara Kazuhiro , Suhara Masamitsu , Matsukura Mitsuru , Isaji Toshihiko , Takayama Toshio
Published: June 2022

Gastroduodenal artery aneurysms (GDAA) and pancreaticoduodenal artery aneurysms (PDAA) are rare, have high rupture risks, and are located in the arcade between the celiac artery and the superior mesenteric artery. Pancreaticoduodenal artery aneurysms are associated with celiac artery stenosis, and it is hypothesized that these celiac lesions might contribute to the formation of aneurysms. In contrast, a few studies have reported an association between a gastroduodenal artery aneurysm and celiac lesions. This study aimed to investigate the potential differences between patients with gastroduodenal and pancreaticoduodenal artery aneurysms and better understand their pathogenesis.

We selected patients with GDAA and PDAA who were admitted to our department between January 2010 and December 2020. Aortic wall volume, aortic wall calcification, and pancreaticoduodenal arcade volume of computed tomography images were calculated semi-manually using Horos 3.3.5.

Eight GDAAs and 11 PDAAs were analyzed. Celiac lesions were found in all PDAA patients, with none in GDAA cases. Volumetry demonstrated that aortic wall volume and calcification were more prominent in the GDAA group than in the PDAA group (P = .026 and P = .049, respectively). The pancreaticoduodenal arcade volume was larger in the PDAA group (P = .002).

In our study, celiac artery lesions were strongly correlated with PDAA. The volume of the pancreaticoduodenal arcade was larger in the PDAA group, and aortic wall volume and calcification were larger in the GDAA group.
Localized Malignant Peritoneal Mesothelioma (LMPeM) in Women: A Clinicopathologic Study of 18 Cases
Authors: Malpica Anais , Euscher Elizabeth D. , Marques-Piubelli Mario L. , Miranda Roberto N. , Raghav Kanwal P. , Fournier Keith F. , Ramalingam Preetha
Published: June 2022

Localized malignant peritoneal mesothelioma is a rare tumor with limited information in the literature. In this study, we present our experience with 18 cases seen in our hospital over a period of 43 years (1978 to 2021). Patients’ median age was 55 years (y) (range: 33 to 79 y) and most of them were Caucasians. Patients presented with abdominal pain (11), ascites and right leg swelling (1), abdominal mass (1), and as incidental finding (1). Thirty percent of patients reported asbestos exposure, and all patients with available information had family history of tumors; a third had personal history of tumors. Seventy-seven percent had some form of abdominopelvic surgery and/or inflammatory process. Most cases had microscopic features typically seen in malignant mesothelioma; however, some cases had confounding features such as signet-ring cells, spindle cells, clear cell changes, and adenomatoid tumor-like appearance. BAP-1 by immunohistochemistry was lost in 1/3 cases. Only 1 patient underwent genetic testing and had an MSH2 germline mutation. Homozygous deletion of CDKN2A by FISH was not found in 1 tested case, although next-generation sequencing identified a CDKN2A pathogenic mutation. 16/18 (88%) had surgical treatment, and some also received adjuvant chemotherapy. The mean overall survival (OS) of our patients was 80.4 months (95% confidence interval: 54.3-106.52); the 3-year OS was 79%, while the 5-year OS was 52.6%. Fifty-three percent of patients had recurrences and 20% had tumor progression. Although the limited sample precludes definitive conclusions, small tumor size, low-grade cytology, and low mitotic index appeared to be associated with an indolent behavior.
Comparison of Preoperative Imaging Modalities for the Assessment of Malignant Potential of Pancreatic Cystic Lesions
Authors: Lee Sang-Woo , Shim Sung Ryul , Jeong Shin Young , Kim Seong-Jang
Published: June 2022

Purpose

The aims of this study are to compare the performance of various preoperative imaging modalities for assessing the malignant potential of pancreatic cystic lesions (PCLs) through a network meta-analysis (NMA) and to clarify the role of 18F-FDG PET in the management of patients with PCL.

Methods

PubMed, EMBASE, and Cochrane Library were searched for the studies evaluating the performance of preoperative imaging modalities for identifying malignant PCLs. The NMA was performed for 4 representative categories of various imaging modalities in terms of diagnostic performance for differentiating malignant from benign PCL and intraductal papillary mucinous neoplasms only as a subgroup analysis. To calculate the probability of each imaging modality being the most effective diagnostic method, the surface under the cumulative ranking curve values were obtained.

Results

A total of 1018 patients from 17 direct comparison studies using 2 or more preoperative imaging modalities were included for differentiating malignant from benign PCL. The positive predictive value (PPV) and accuracy of 18F-FDG PET were significantly higher than that of CT (PPV: odds ratio [OR], 2.66; 95% credible interval [CrI], 1.21–6.17; accuracy: OR, 2.63; 95% CrI, 1.41–5.38) or MRI (PPV: OR, 2.50; 95% CrI, 1.09–6.26; accuracy: OR, 2.50; 95% CrI, 1.28–5.47) in all PCLs, as well as in the subgroup analysis for intraductal papillary mucinous neoplasm only. 18F-FDG PET showed the highest surface under the cumulative ranking curve values in all diagnostic performance areas of sensitivity, specificity, PPV, negative predictive value, and accuracy, followed by MRI or CT.

Conclusions

The results from this NMA suggest that 18F-FDG PET is the best preoperative imaging modality for differentiating malignant from benign PCLs and that it can be used for the preoperative evaluation of PCLs.
Establishing national stakeholder priorities for quality improvement in pediatric trauma care: Consensus results using a modified Delphi process
Authors: Melhado Caroline G. , Yorkgitis Brian K. , Patel Bhavin , Remick Katherine , Macias Charles G. , Dingeldein Michael W. , Gray Lisa , Jensen Aaron R.
Published: June 2022

BACKGROUND

Quality improvement efforts within pediatric trauma centers (PTCs) are robust, but the majority of children do not receive initial postinjury care at PTCs. Disparities in access to quality trauma care remain, particularly for children who initially access the trauma system outside of a PTC. The purpose of this project was to identify unmet needs for injured children within the pediatric emergency care system and to determine national priorities for quality improvement across the continuum of pediatric trauma care.

METHODS

A panel of delegates representing patients and families, prehospital providers, federal funding partners, nurses, and physicians was recruited from 10 national stakeholder organizations. Potential targets were identified using an initial stakeholder meeting followed by a free text response survey. Free text items were coded and condensed as themes and then ranked by the panel using a modified Delphi approach to determine consensus priorities. Items not achieving >35% prioritization on a given iteration were dropped from subsequent iterations. Consensus was defined as 75% of members designating an item as a top-four priority.

RESULTS

Nineteen themes were identified as potential targets for QI initiatives. Four iterations of panel ranking were used to achieve consensus, with four priorities identified: (1) creation of a toolkit and standard provider training for pediatric trauma triage, shock recognition, and early recognition for need to transfer to higher level of care; (2) development of minimum standards for pediatric trauma resuscitation and stabilization capability in nonpediatric centers; (3) facilitating creation of local nursing and physician champions for pediatric trauma; and (4) development and dissemination of best-practice guidelines to improve imaging practices for injured children.

CONCLUSION

System-level quality improvement priorities for pediatric trauma care should focus resources on developing and implementing minimum pediatric standards for injury care, frontline provider training, stabilization protocols, imaging guidelines, and local pediatric champions.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Clinical Utility in Adopting Race-free Kidney Donor Risk Index
Authors: Doshi Mona D. , Schaubel Douglas E. , Xu Yuwen , Rao Panduranga S. , Sung Randall S.
Published: June 2022

Background.

Recent events of racial injustice prompted us to study potential impact of removing race from kidney donor risk index (KDRI) calculator.

Methods.

We used Scientific Registry for Transplant Recipients data to analyze outcomes of 66 987 deceased-donor kidney transplants performed in the United States between 2010 and 2016. Graft failure (GF) was defined as death or return to dialysis or requiring repeat transplant. We compared original KDRI and a race-free KDRI (Black donor coefficient zeroed out in the KDRI formula) with respect to recategorization of perceived GF risk (based on KDPI categories: ≤20, 21–34, 35–85, ≥86)‚ risk discrimination (using the C statistic) and predictive accuracy (using Brier score), and GF risk prediction (using Cox regression on time-to-GF). We used logistic regression to study the impact of donor race on discard probability.

Results.

There were 10 949 (16.3% of recipients) GF, and 1893 (17% of GFs) were among recipients of kidneys from Black donors. The use of race-free KDRI resulted in reclassification of 49% of kidneys from Black donors into lower GF risk categories. The impact on GF risk discrimination was minimal, with a relative decrease in C statistic of 0.16% and a change in GF predictive accuracy of 0.07%. For a given recipient/donor combination, transplants from Black (compared with non-Black) donors are estimated to decrease predicted graft survival at 1-y by 0.3%–3%, and 5-y by 1%–6%. Kidneys from Black donors are significantly more likely to be discarded (odds ratio adjusted for KDRI except race = 1.24). We estimate that an equal discard probability for Black and non-Black donors would yield 70 additional kidney transplants annually from Black donors.

Conclusions.

Use of race-free KDRI did not impact GF risk discrimination or predictive accuracy and may lower discard of kidneys from Black donors. We recommend use of race-free KDRI calculator acknowledging the possibility of miscalculation of GF risk in small proportion of kidneys from Black donors.
A GPU-based computational framework that bridges Neuron simulation and Artificial Intelligence
Authors: Zhang Yichen , He Gan , Liu Xiaofei , Johannes Hjorth J.J. , Kozlov Alexander , He Yutao , Zhang Shenjian , Ma Lei , Kotaleski Jeanette Hellgren , Tian Yonghong , Grillner Sten , Du Kai , Huang Tiejun
Published: June 2022

Biophysically detailed multi-compartment models are powerful tools to explore computational principles of the brain and also serve as a theoretical framework to generate algorithms for artificial intelligence (AI) systems. However, the expensive computational cost severely limits the applications in both the neuroscience and AI fields. The major bottleneck during simulating detailed compartment models is the ability of a simulator to solve large systems of linear equations. Here, we present a novel Dendritic Hierarchical Scheduling (DHS) method to markedly accelerate such process. We theoretically prove that the DHS implementation is computationally optimal and accurate. This GPU-based method performs at 2-3 orders of magnitude higher speed than that of the classic serial Hines method in the conventional CPU platform. We build a DeepDendrite framework, which integrates the DHS method and the GPU computing engine of the NEURON simulator and demonstrate applications of DeepDendrite in neuroscience and AI tasks. We investigated how spatial patterns of spine inputs affect neuronal excitability in a detailed human pyramidal neuron model with 25,000 spines; and examined how dendrites protect morphologically detailed neural networks against adversarial attacks in typical image classification tasks.
Wide-Field Stokes Polarimetric Microscopy for Second Harmonic Generation Imaging
Authors: Castaño Leonardo Uribe , Mirsanaye Kamdin , Kontenis Lukas , Krouglov Serguei , Akens Margarete K. , Barzda Virginijus
Published: June 2022

We employ wide-field second harmonic generation (SHG) microscopy together with nonlinear Stokes polarimetry for quick ultrastructural investigation of large sample areas (700μmx 700μm) in thin histology sections. The Stokes vector components for SHG are obtained from the polarimetric measurements with incident and outgoing linear and circular polarization states. The Stokes components are used to construct the images of polarimetric parameters and deduce the sample maps of achiral and chiral nonlinear susceptibility tensor components ratios and cylindrical axis orientation in fibrillar materials. The imaged histology sections with polarimetric wide-field SHG microscopy provide large area maps of ultrastructural information about the collagenous tissue, which can be used for rapid histology investigations.
Fossil-explorer.com: An efficient interactive approach to exploring fossil data
Authors: Wu Junqi , Xu Honghe , Pan Zhaohui , Niu Zhibin
Published: June 2022

Fossils today are increasingly being digitized and documented by multi-modal data obtained from visual data (i.e., photos and tomographic images), as well as text, locations, geological ages, and other chemical and physical measurements. Popular online websites such as PBDB and GBDB offer visual explorations of specimens’ localities, but they have limited multi-modal data visualization abilities and face challenges related to visual obscuration and insufficient interaction/exploration. Here, we present fossil-explorer.com, a continuously developing open-source online tool for assisting paleontologists with interactively exploring fossil collections. The tool is designed to address the issues of visual clutter, limited data types, and insufficient interactions. It is intuitive and endorsed by paleontologists. We have also quantitatively evaluated the tool by measuring the interaction scaling performance. The results show that it providessublinear interaction performanceand thus is able to deal efficiently with millions-level data. The currentfossil-explorer.comdemonstrates the Ordovician to Silurian graptolite fossil multimedia dataset, which is significant in global stratigraphy and shale gas exploration. The extended version also facilitates the use of Deepbone (http://deepbone.org), world’s most comprehensive database of vertebrate paleontology database. We developed the code forfossil-explorer.comto be open access and will continue to improve it.
A multiomics comparison of weight loss interventions shows the distinct effects of bariatric surgery and intermittent fasting on hepatic metabolism
Authors: Haran Arnon , Bergel Michael , Kleiman Doron , Hefetz Liron , Israeli Hadar , Weksler-Zangen Sarah , Agranovich Bella , Abramovich Ifat , Schyr Rachel Ben-Haroush , Gottlieb Eyal , Ben-Zvi Danny
Published: June 2022

The prevalence of obesity and non-alcoholic fatty liver (NAFL) is steadily increasing. Weight loss can lead to improvement in NAFL in patients and in model organisms. Weight loss can be achieved through either dietary and lifestyle interventions, pharmacotherapy, and bariatric surgery. Some interventions, such as intermittent fasting, have been purported to have benefits beyond those conferred by weight loss alone.

In this study, rats were provided a high-fat, high-sucrose diet for 7 weeks and then were assigned to strict caloric restriction with intermittent fasting (IF-CR) or to sleeve gastrectomy (SG) bariatric surgery, achieving equivalent weight loss. The two interventions were compared to ad-libitum fed controls. The metabolome of the blood entering the liver was analyzed in the three experimental groups, as well as the metabolome and transcriptome of the liver under fasting conditions, to test how different means of weight loss affect the input of the liver and hepatic metabolism.

Surprisingly, the two interventions had different and often opposite effects on the composition of portal blood and liver metabolites. IF-CR resulted in sweeping changes across multiple central metabolic pathways, including an increase in de novo lipogenesis and triglyceride export, and upregulation of glycolysis, citric acid cycle, and the pentose phosphate pathway, as well as an increase in glycogen storage. Meanwhile, the effects of SG concentrated on one-carbon metabolic pathways, with changes in metabolite and transcript levels pointing to decreased transmethylation and methionine cycle activity, with downstream effects on levels of glutathione and the hepatic oxidative state.

In conclusion, our study highlights how different means of weight loss affect distinct metabolic pathways and demonstrates a unique effect of bariatric surgery on hepatic one-carbon and redox pathways.
G-quadruplex recognition by DARPIns through epitope/paratope analogy
Authors: Miclot Tom , Bignon Emmanuelle , Terenzi Alessio , Grandemange Stéphanie , Barone Giampaolo , Monari Antonio
Published: June 2022

We investigated the mechanisms leading to the specific recognition of Guanine Guadruplex (G4) by DARPins peptides, which can lead to the design of G4s specific sensors. To this end we carried out all-atom molecular dynamic simulations to unravel the interactions between specific nucleic acids, including human-telomeric (h-telo), Bcl-2, and c-Myc, with different peptides, forming a DARPin/G4 complex. By comparing the sequences of DARPin with that of a peptide known for its high affinity for c-Myc, we show that the recognition cannot be ascribed to sequence similarity but, instead, depends on the complementarity between the three-dimensional arrangement of the molecular fragments involved: the α-helix/loops domain of DARPin and the G4 backbone. Our results reveal that DARPins tertiary structure presents a charged hollow region in which G4 can be hosted, thus the more complementary the structural shapes, the more stable the interaction.
Dose-dependent suppression of hippocampal contextual memory formation, place cells, and spatial engrams by the NMDAR antagonist (R)-CPP
Authors: Zhu Mengwen , Perkins Mark G. , Lennertz Richard , Abdulzahir Alifayez , Pearce Robert A.
Published: June 2022

A common way to study the functional importance of N-methyl-D-aspartate receptors (NMDARs) in hippocampal memory-encoding circuits is by administering NMDAR antagonists. We recently compared the effects of (R,S)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a competitive NMDAR antagonist, on suppression of memory in vivo versus suppression of NMDAR-mediated field EPSPs (fEPSPNMDA) and long-term potentiation (LTP) in vitro. Surprisingly, we found that concentrations that block contextual conditioning in vivo are ineffective at blocking the fEPSPNMDA or LTP in vitro. Here we tested one possible explanation for the mismatch – that the hippocampus is relatively resistant to CPP compared to other brain structures engaged in contextual fear conditioning. We used the context pre-exposure facilitation effect (CPFE) paradigm to isolate the hippocampal component of contextual learning, and in-vivo calcium imaging of place cells and spatial engrams to directly assess hippocampal spatial coding. We found that, by both measures, the active enantiomer (R)-CPP did interfere with hippocampal function at concentrations below those that block fEPSPs or LTP. We conclude that the alternative – that CPP interferes with memory by targeting NMDARs in interneurons rather than pyramidal neurons – is the more likely explanation.
Simulation of Energy Regeneration in Human Locomotion for Efficient Exoskeleton Actuation
Authors: Laschowski Brokoslaw , Inkol Keaton A. , Mihailidis Alex , McPhee John
Published: June 2022

Backdriveable actuators with energy regeneration can improve the efficiency and extend the battery-powered operating times of robotic lower-limb exoskeletons by converting some of the otherwise dissipated energy during negative mechanical work into electrical energy. However, previous related studies have focused on steady-state level-ground walking. To better encompass real-world community mobility, here we developed a feedforward human-exoskeleton energy regeneration system model to simulate energy regeneration and storage during other daily locomotor activities. Data from inverse dynamics analyses of 10 healthy young adults walking at variable speeds and slopes were used to calculate the negative joint mechanical power and work (i.e., the mechanical energy theoretically available for electrical energy regeneration). These human joint mechanical energetics were then used to simulate backdriving a robotic exoskeleton and regenerating energy. An empirical characterization of the exoskeleton device was carried out using a joint dynamometer system and an electromechanical motor model to calculate the actuator efficiency and to simulate energy regeneration. Our performance calculations showed that regenerating energy at slower walking speeds and decline slopes could significantly extend the battery-powered operating times of robotic lower-limb exoskeletons (i.e., up to 99% increase in total number of steps), therein improving locomotor efficiency.
Comprehensive Characterisation of Fetal and Mature Retinal Cell Identity to Assess the Fidelity of Retinal Organoids
Authors: Kim Hani Jieun , O’Hara-Wright Michelle , Kim Daniel , Loi To Ha , Lim Benjamin Y. , Jamieson Robyn V. , Gonzalez-Cordero Anai , Yang Pengyi
Published: June 2022

Characterizing cell identity in complex tissues such as the human retina is essential for studying its development and disease. While retinal organoids derived from pluripotent stem cells have been widely used to model development and disease of the human retina, there is a lack of studies that have systematically evaluated molecular and cellular fidelity of the organoids derived from various culture protocols in recapitulating their in vivo counterpart. To this end, we performed an extensive meta-atlas characterisation of cellular identities of the human eye, covering a wide range of developmental stages. The resulting map uncovered previously unknown biomarkers of major retinal cell types and those associated with cell-type specific maturation. Using our retinal cell identity map from the fetal and adult tissues, we systematically assessed the fidelity of the retinal organoids to mimic the human eye, enabling us to comprehensively benchmark the current protocols for retinal organoid generation.
On the Interaction of Biopotential Sensing and Right Leg Drive System with Electro-Quasistatic Human Body Communication
Authors: Sriram Shreeya , Polachan Kurian , Sen Shreyas
Published: June 2022

Continuous long-term sensing of biopotential signals is vital to facilitate accurate diagnosis. The current state of the art in wearable health monitoring relies on radiative technology for communication. Due to their radiative nature, these systems result in lossy and inefficient transmission, limiting the device’s life span. Human Body Communication has emerged as an energy-efficient secure communication modality, and literature has shown body communication to transmit biopotential signals at 100x lower power than traditional radiative technologies. Unlike radiative communication that uses airwaves, HBC, specifically Capacitive Electro-Quasistatic HBC (EQS-HBC), couple signals and confine them within the human body. In Capacitive EQS-HBC, the transmitter uses an electrode to modulate the body potential to transmit data. The modulation of body potential by HBC raises the following concerns. Will HBC transmissions affect the quality of biopotential signals sensed from the body? Additionally, since biopotential sensing systems commonly use Right Leg Drive (RLD) to bias body potential, there is also a concern if RLD can affect the quality of HBC transmissions.

For the first time, our work studies the interactions between EQS-HBC and biopotential sensing. Our work is important since understanding HBC-RLD interactions is integral to developing EQS-HBC-based biosensors for Body Area Networks (BANs). For the studies, we conducted lab experiments and developed circuit theoretic models to back the experimental outcomes. We show that due to their higher frequency content and common-mode nature, HBC transmissions do not affect the differential sensing of low-frequency biopotential signals. We show that biopotential sensing using RLD affects HBC. RLD deteriorates the signal strength of HBC transmissions. We thus propose not to use RLD with HBC. We demonstrate our proposed solution by transmitting ECG signals using HBC with 96% correlation compared to the traditional wireless system at a fraction of the power.
Methamphetamine induced regional-specific transcriptomic and epigenetic changes in the rat brain
Authors: Miao Benpeng , Xing Xiaoyun , Bazylianska Viktoriia , Madden Pamela , Moszczynska Anna , Zhang Bo
Published: June 2022

Background

Methamphetamine (METH) is a highly addictive central nervous system stimulant. Chronic use of METH is associated with multiple neurological and psychiatric disorders. An overdose of METH can cause brain damage and even death. Mounting evidence indicates that epigenetic changes and functional impairment in the brain occur due to addictive drug exposures. However, the responses of different brain regions to a METH overdose remain unclear.

Results

We investigated the transcriptomic and epigenetic responses to a METH overdose in four regions of the rat brain, including the nucleus accumbens, dentate gyrus, Ammon’s horn, and subventricular zone. We found that 24 hours after METH overdose, 15.6% of genes showed changes in expression and 27.6% of open chromatin regions exhibited altered chromatin accessibility in all four rat brain regions. Interestingly, only a few of those differentially expressed genes and differentially accessible regions were affected simultaneously. Among four rat brain regions analyzed, 149 transcription factors and 31 epigenetic factors were significantly affected by METH overdose. METH overdose also resulted in opposite-direction changes in regulation patterns of both gene and chromatin accessibility between the dentate gyrus and Ammon’s horn. Approximately 70% of chromatin-accessible regions with METH-induced alterations in the rat brain are conserved at the sequence level in the human genome, and they are highly enriched in neurological processes. Many of these conserved regions are active brain-specific enhancers and harbor SNPs associated with human neurological functions and diseases.

Conclusion

Our results indicate strong region-specific transcriptomic and epigenetic responses to a METH overdose in distinct rat brain regions. We describe the conservation of region-specific gene regulatory networks associated with METH overdose. Overall, our study provides clues toward a better understanding of the molecular responses to METH overdose in the human brain.
Do training with blurred images make convolutional neural networks closer to humans concerning object recognition performance and internal representations?
Authors: Yoshihara Sou , Fukiage Taiki , Nishida Shin’ya
Published: June 2022

Abstract

It is suggested that experiences of perceiving blurry images in addition to sharp images contribute to the development of robust human visual processing. To computationally investigate the effect of exposure to blurry images, we trained Convolutional Neural Networks (CNNs) on ImageNet object recognition with a variety of combinations of sharp and blurry images. In agreement with related studies, mixed training on sharp and blurred images (B+S) makes the CNNs close to humans with respect to robust object recognition against a change in image blur. B+S training also reduces the texture bias of CNN in recognition of shape-texture-cue-conflict images, but the effect is not strong enough to achieve a strong shape bias comparable to what humans show. Other tests also suggest that B+S training is not sufficient to produce robust human-like object recognition based on global con-figurational features. We also show using representational similarity analysis and zero-shot transfer learning that B+S-Net does not acquire blur-robust object recognition through separate specialized sub-networks, each for sharp and blurry images, but through a single network analyzing common image features. However, blur training alone does not automatically create a mechanism like the human brain where subband information is integrated into a common representation. Our analyses suggest that experience with blurred images helps the human brain develop neural networks that robustly recognize the surrounding world, but it is not powerful enough to fill a large gap between humans and CNNs.
Inequalities in children’s mental health care: analysis of routinely collected data on prescribing and referrals to secondary care
Authors: Ball William P , Black Corri , Gordon Sharon , Ostrovska Bārbala , Paranjothy Shantini , Rasalam Adelene , Ritchie David , Rowlands Helen , Rzewuska Magdalena , Thompson Elaine , Wilde Katie , Butler Jessica E
Published: June 2022

Background

One in eight children in the United Kingdom are estimated to have a mental health condition, and many do not receive support or treatment. The COVID-19 pandemic has negatively impacted mental health and disrupted the delivery of care. Prevalence of poor mental health is not evenly distributed across age groups, by sex or socioeconomic groups. Equity in access to mental health care is a policy priority but detailed socio-deomgraphic trends are relatively under-researched.

Methods

We analysed records for all mental health prescriptions and referrals to specialist mental health outpatient care between the years of 2015 and 2021 for children aged 2 to 17 years in a single NHS Scotland health board region. We analysed trends in prescribing, referrals, and acceptance to out-patient treatment over time, and measured differences in treatment and service use rates by age, sex, and area deprivation.

Results

We identified 18,732 children with 178,657 mental health prescriptions and 21,874 referrals to specialist outpatient care. Prescriptions increased by 59% over the study period. Boys received double the prescriptions of girls and the rate of prescribing in the most deprived areas was double that in the least deprived. Mean age at first mental health prescription was almost 1 year younger in the most deprived areas than in the least. Referrals increased 9% overall. Initially, boys and girls both had an annual referral rate of 2.7 per 1,000, but this fell 6% for boys and rose 25% for girls. Referral rate for the youngest decreased 67% but increased 21% for the oldest. The proportion of rejected referrals increased steeply since 2020 from 17% to 30%. The proportion of referrals accepted for girls rose to 62% and the mean age increased 1.5 years.

Conclusions

The large increase in mental health prescribing and changes in referrals to specialist outpatient care aligns with emerging evidence of increasing poor mental health, particularly since the start of the COVID-19 pandemic. The static size of the population accepted for specialist treatment amid greater demand, and the changing demographics of those accepted, indicate clinical prioritisation and unmet need. Persistent inequities in mental health prescribing and referrals require urgent action.
Pharmaco-Pheno-Multiomic Integration Reveals Biomarker Profiles and Therapeutic Response Prediction Models in Leukemia and Ovarian Cancer
Authors: Silberberg Gilad , Walling Brandon , Wesa Amy , Audia Alessandra , Sloma Ido , Zeng Yi , Han Guanghui , Tang Jia , Pammer Paige , Bakayoko A’ishah , Ren Xuan , Ciznadija Daniel , Vishwakarma Bandana , Mosesson Yaron , Zipeto Marianna , Ritchie Michael
Published: June 2022

Despite considerable progress made in improving therapeutic strategies, the overall survival for patients diagnosed with various cancer types remains low. Further, patients often cycle through multiple therapeutic options before finding an effective regimen for the specific malignancy being treated. A focus on building enhanced computational models, which prioritize therapeutic regimens based on a tumor’s complete molecular profile, will improve the patient experience and augment initial outcomes. In this study, we present an integrative analysis of multiple omic datasets coupled with phenotypic and therapeutic response profiles of Cytarabine from a cohort of primary AML tumors, and Olaparib from a cohort of Patient-Derived Xenograft (PDX) models of ovarian cancer. These analyses, termed Pharmaco-Pheno-Multiomic (PPMO) Integration, established novel complex biomarker profiles that were used to accurately predict prospective therapeutic response profiles in cohorts of newly profiled AML and ovarian tumors. Results from the computational analyses also provide new insights into disease etiology and the mechanisms of therapeutic resistance. Collectively, this study provides proof-of-concept in the use of PPMO to establish highly accurate predictive models of therapeutic response, and the power of leveraging this method to unveil cancer disease mechanisms.
In Silico insight to identify Potential Inhibitors of BUB1B from Mushroom bioactive compounds to Prevent Breast cancer metastasis
Authors: Mishra Divya , Mishra Ashish , Singh M.P.
Published: June 2022

BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) gene belongs to the spindle assembly checkpoint protein family, proven to be associated with many kinds of cancers. Protein kinases are crucial in metaphase to anaphase cellular transition. It is a primary element of spindle assembly checkpoint (SAC). This SAC is responsible for guarding the proper chromosomal segregation while any chromosomal instability hinders its normal functioning. The chromosomal instability may lead to cancer progression. And it occurs mainly due to overexpression of BUB1B in many cancer types especially in breast cancer metastasis. This could be controlled by designing proper inhibitor of this gene. For this purpose, there are proved existence of various mushroom compounds possessing some important medicinal properties with proven anti- cancerous effects. Proper screening and identification of molecules having these anti-cancerous effects and showing affinity against BUB1B with inhibition properties could be obtained from these compounds. So this study has incorporated 70 bioactive compounds (handpicked through literature mining) of distinct mushrooms that were considered and explored for identifying a suitable drug candidate. Their ADME/T properties were obtained to predict the drug-likeness of these 70 mushroom compounds based on Lipinski’s rule of 5 (RO5). The screening of these bioactive compounds and subsequent molecular docking against BUB1B provided compounds with the best conformation-based binding affinity. The best 2 complexes, i.e., BUB1B- Lepiotaprocerin D and BUB1B-Peptidoglycan, were subjected to the molecular dynamics simulation. Both the complexes were observed for their affinity, stability, and flexibility in protein-ligand complex systems. The MD simulation study revealed that Lepiotaprocerin D has an energetically favorable binding affinity with BUB1B. Results showed that the formation of a hydrogen bond between ASN123, SER157 residue and Lepiotaprocerin D has strengthened the affinity of Lepiotaprocerin D with BUB1B. Hence, this study identified Lepiotaprocerin D as a potential and novel inhibitor for BUB1B that could be a plausible drug candidate for checking and controlling the spread of breast cancer metastasis.
The application of neural networks to classify dolphin echolocation clicks
Authors: Seydi Vahid , Chapuis Lucille , Veneruso Gemma , Balaguru Sudha , Bristow Noel , Mills David , Le Vay Lewis
Published: June 2022

Passive acoustic monitoring (PAM) is a common approach to monitor marine mammal populations, for species of dolphins, porpoises and whales that use sound for navigation, feeding and communication. PAM produces large datasets which benefit from the application of machine learning algorithms to automatically detect and classify the vocalisations of these animals. We present a deep learning approach for the classification of dolphins’ echolocation clicks into two species groups in an environment with high background noise. We compare the use of Convolutional Neural Networks (CNN) and Recurrent Neural Network (RNN), in which we feed the models the raw waveform data and spectrograms. We show that both models perform well, with the highest performance achieved by a CNN fed with spectrograms (F1 score 97 %) and an RNN fed with raw data (F1 score 96%) fitted with Gated Recurrent Units (GRU). We recommend the use of such models to classify echolocation clicks in marine environments where background noise levels exhibit high spatial and temporal variance. In particular, the RNN showed excellent performance, while being fed with raw data, in terms of reduced processing time and storage. Deep learning automatically extracts effective features from the raw waveform in the training process through multiple layers of the model, without the need to rely on feature extraction in a separate pre-processing step.