bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and etiology of Helicobacter pylori infection in dyspepsia patients: a hospital-based cross-sectional study
Authors: Sardar Maryam , Kumar Deepak , Aakash FNU , Partab FNU , Kumar Sunny , Barkha FNU , Danesh FNU , Berza Qammer , Shaikh Bisma , Sangam FNU , Hasan Mohammad , Erum Sheeza , Mumtaz Hassan
Published: April 2023

Background:

Helicobacter pylori infection is seropositive in ~50% of people globally. Therefore, this study was conducted to evaluate its prevalence in dyspepsia patients.

Methods:

A cross-sectional study was conducted at Jinnah Postgraduate Medical Centre (JPMC) from January to June 2022 to find out the prevalence and risk factors of H. pylori in dyspepsia patients. A prevalidated questionnaire was used to collect the data from 180 patients. This study adheres to the principles outlined in the Helsinki Declaration. The χ
2-test was applied, and the odds ratio and 95% CI were calculated to find the association of H. pylori with the risk factors.

Results:

A total of 180 patients were enrolled in this study, of whom, 73 (40.6%) patients were male and 107 (59.4%) were female. In seropositive H. pylori patients, 80 (60.6%) patients had nausea or vomiting, 110 (83.3%) patients were found to have flatulence, 128 (97.7%) patients were experiencing frequent burping, and 114 (86.4%) patients were having epigastric pain. The household member greater than 4, smoking, rural area residence, NSAIDs consumption, BMI greater than 25, O+ blood group, and Rhesus positive status were significantly associated with H. pylori with a P value of less than 0.05.

Conclusion:

This study concludes that the prevalence of H. pylori in our population is high, and the risk factors identified are lower class, BMI greater than 25, smoking, O+ blood group, NSAID consumption, rural area residence, household member greater than 4, Rhesus positive status, and the symptoms of nausea or vomiting, frequent burping, epigastric pain, and flatulence. Patients with an increased number of risk factors should be taken into consideration for an appropriate checkup.
Parasitological and histopathological features of appendectomy specimens in Fars Province, southern Iran: a retrospective study
Authors: Mohtasebi Sina , Shokripour Mansoureh , Vahid Parisa , Mikaeili Fattaneh , Abbaszadeh Afshar Mohammad Javad , Alimi Rasoul , Goudarzi Fatemeh , Teimouri Aref
Published: April 2023

Background:

Although the appendix is the most commonly resected and examined intra-abdominal organ, the pathogenesis and etiology of acute nonspecific appendicitis remain enigmatic. This retrospective study aimed to assess the prevalence of parasitic infection in surgically removed appendices and to evaluate the probable associations between the presence of parasites and the occurrence of appendicitis through parasitological and histopathological examinations of the appendectomy specimens.

Materials and methods:

This retrospective study was carried out from April 2016 to March 2021 among all patients referred to hospitals affiliated with Shiraz University of Medical Sciences, Fars Province, Iran, for appendectomy. Patient information, including age, sex, year of appendectomy, and type of appendicitis, was collected from the available data in the hospital information system database. In positive cases, all pathology reports were retrospectively evaluated for the presence of the parasite and its type, and analytical and descriptive statistics were carried out using SPSS software version 22.

Results:

A total of 7628 appendectomy materials were evaluated in the present study. Of the total participants, 4528 (59.4%, 95% CI: 58.2–60.5) were males, and 3100 (40.6%, 95% CI: 39.5–41.8) were females. The mean age of participants was 23.87±14.28 years. Overall, Enterobius vermicularis was observed in 20 appendectomy specimens. Fourteen of these patients (70%) were less than 20 years old.

Conclusion:

This study indicated that E. vermicularis is one of the common infectious agents that could be found in the appendix and may increase the risk of appendicitis. Therefore, in terms of appendicitis, clinicians, and pathologists must be aware of the possible presence of parasitic agents, especially E. vermicularis, to treat and manage the patients sufficiently.
Normal preoperative levels of gamma-glutamyltransferase predict the absence of common bile duct stones in patients scheduled for laparoscopic cholecystectomy: a retrospective cohort study
Authors: Khan Noman Ahmed , Siraj Muhammad Imran , Rajput Iqra Anees , Memon Zahid Ali , Ali Rehan Ramzan , Ursani Asna , Anees Muhammad Muthar , Kumar Karan , Naina  , Kumar Rahul Robaish , Kumar Rahul , Shahab Ramsha , Asghar Muhammad Sohaib
Published: April 2023

Objective:

Laparoscopic cholecystectomy, nowadays, is considered the gold standard option for management in patients diagnosed with symptomatic cholelithiasis. Nevertheless, some patients may have coexisting choledocholithiasis, which manifests later in life with grave complications such as cholangitis and pancreatitis. The objective of this study is to evaluate the role of preoperative gamma-glutamyltransferase (GGT) in predicting choledocholithiasis in patients undergoing laparoscopic cholecystectomy.

Method:

A total of 360 patients with symptomatic cholelithiasis based on diagnosis aided with abdominal ultrasound were included in the study. The study design was a retrospective cohort. Patients were evaluated based on a comparison between findings of per-operative cholangiogram and laboratory measure of GGT.

Result:

The mean age of study participants was 47.22 (±28.41) years. Mean GGT levels were 121.54 (±87.91) U/l. One hundred (27.7%) participants had raised GGT. But only 19.4% had been diagnosed with filling defect positive on cholangiogram. The predictability of GGT for positive cholangiogram is statistically significant at less than 0.001 with an area under the curve of 0.922 (0.887–0.957), sensitivity of 95.7%, specificity of 88.6%, and accuracy of 90%. The standard error reported (0.018) was found to be relatively low.

Conclusion:

Based on the provided information, it is concluded that GGT plays an important role in predicting the coexistence of choledocholithiasis in symptomatic cholelithiasis and can be used in the setting where the facility of per-operative cholangiogram is not available.
Pubertal extravaginal nontraumatic spontaneous testicular torsion: a case report
Authors: Basukala Sunil , Rayamajhi Bikash Bikram , Karki Sabin , Shrestha Melina , Banmala Sabin , Maharjan Suman
Published: April 2023

Introduction and Importance:

Testicular torsion (TT) is the most common urosurgical emergency in the case of acute scrotal pain. Early diagnosis, both clinically with imaging and emergent surgical exploration, is the key step in the salvage of testis and its management.

Case Presentation:

A 12-year-old male with no known comorbidities came to the emergency department of our center with complaints of left scrotal region pain and swelling for 10 h.

Clinical Findings and Investigation:

Left testicular tenderness and swelling with Phren’s sign negative, Deming’s sign positive, and absent cremasteric reflex. Ultrasonography showed coarse echotexture with a lack of obvious vascularity in the left testicle suggestive of TT and bulky left epididymis with bilateral hydrocele; left side greater than right.

Intervention and Outcome:

The patient underwent emergency left orchidectomy with right orchidopexy. Following this, he was symptomatically better, and the excruciating testicular pain and swelling subsided.

Conclusion:

Extravaginal TT is a rare presentation in pubertal age groups; however, whatever may be the types and causes, TT is a urological emergency that may lead to permanent ischemic necrosis. Delays in diagnosis should be avoided as this is directly related to the percentage of testicular salvage or loss. Prompt emergent surgical exploration is the cardinal point in management.
L-2-hydroxyglutaric aciduria – review of literature and case series
Authors: Ahmed Sibtain , Siddiqui Ayra , DeBerardinis Ralph J. , Ni Min , Gu Lai Wen , Cai Feng , Vu Hieu S. , Afroze Bushra
Published: April 2023

Background:

L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive, slowly progressive neurodegenerative disease characterized by psychomotor delay and cerebellar dysfunction. The biochemical hallmark is increased concentrations of L2HG in body fluids. Brain MRI exhibits characteristic centripetal extension of the white matter involvement that differentiates it from other leukodystrophies. The authors report two sisters from Pakistan with L2HGA with 4 years of follow-up. The authors have also compared the clinical outcome of our patients with 45 previously reported patients with L2HGA for whom treatment and clinical outcome was reported.

Case presentation:

The authors report two sisters with L2HGA from Pakistan born to consanguineous parents. The 15- and 17-year-old girls presented with psychomotor delay, seizures, ataxia, intentional tremors, and dysarthria. Both had normal anthropometric measurements for age. Exaggerated tendon reflexes and bilateral sustained ankle clonus were observed in addition to cerebellar signs. Urine organic acids analysis showed marked excretion of 2-hydroxyglutaric acid, chiral differentiation of 2-hydroxyglutaric acid showed it to be L2HGA. Brain MRI of the 15-year-old showed diffuse subcortical white matter changes evident by T2/FLAIR hyperintense signals bilaterally, particularly in the frontal region in the centripetal distribution with some diffusion restriction along involvement of globus pallidus. The characteristic MRI pattern raised the suspicion of L2HGA. Targeted L2HGDH sequencing identified a homozygous pathogenic variant, c.829C>T (p.Arg227*) in L2HGDH gene in both girls. Both parents were heterozygous carriers of the familial variant.

Conclusion:

Neuroradiological features of centripetal subcortical leukoencephalopathy with basal ganglia and dentate nuclei involvement are rather specific to L2HGA and should lead to further biochemical investigations to look for L2HGA and L2HGDH gene sequencing.
Cyclosporine treatment for steroid-resistant nephrosis complicated with acquired hemophilia A: a case report
Authors: Alsultan Mohammad , Jomaa Hiba , Shukri Arwa , Hajij Fatima , Hassan Qussai
Published: April 2023

Introduction:

Acquired hemophilia refers to the development of a clotting factor deficiency typically, when autoantibodies are produced against coagulation factor and tend to be in the elderly and rare in children.

Case report:

A 12-year-old girl with steroid-resistant nephrosis (SRN) was admitted complaining of pain in her right leg and an ultrasound showed a hematoma in her right calf. The coagulation profile revealed partial thromboplastin time prolongation and high titers (156 BU) of anti-factor VIII inhibitors were observed. Where half of the patients with antifactor VIII inhibitors were associated with underlying disorders, additional tests were performed that rule out secondary causes. This patient with long-standing SRN, who was on a maintenance dose of prednisone for six years, was complicated with acquired hemophilia A (AHA). In different to the last recommendations of AHA treatment, we preferred using cyclosporine; which is considered the initial second-line therapy for children with SRN. Complete remission was achieved of both disorders after a month with no recurrence of nephrosis or bleeding events.

Conclusion:

To our knowledge, nephrotic syndrome with AHA was reported in only three patients, two cases after remission and one during a relapse but no one were treated with cyclosporine. The authors encountered the first case of cyclosporine treatment for AHA in a patient with SRN. This study supports the use of cyclosporine to treat AHA, especially with nephrosis.
Effects of heated tobacco products and conventional cigarettes on dental implant wound healing: experimental research
Authors: Morishita Yoshihisa , Hasegawa Shogo , Koie Shin , Nakaya Sanako , Goto Mitsuo , Miyachi Hitoshi , Naruse Keiko , Nakamura Nobuhisa , Hayashi Tatsuhide , Kawai Tatsushi , Nagao Toru
Published: April 2023

Background:

Smoking affects wound healing and is associated with dental implant failure. Heated tobacco products (HTPs) appear to be less harmful than conventional cigarettes (CCs); however, there is limited analytical data to support this claim. This study aimed to compare HTPs and CCs for their impact on wound healing using L929 mouse fibroblast cells and evaluate whether HTPs also lead to failure in implant therapy.

Materials and methods:

Cigarette smoke extract (CSE) was obtained from CCs (Marlboro, Philip Morris) and HTPs (Marlboro Heat Sticks Regular for IQOS, Philip Morris) and initiated a wound-healing assay with a cell-free area created in the centre of a titanium plate by sticking a 2-mm-width line tape. The L929 mouse fibroblast cells were exposed with 2.5 and 5% CSE from HTPs and CCs and then seeded in the titanium plate. A scratch wound-healing assay was initiated when all samples were at 80% confluence. The number of cells migrating to the wound site was counted after 12, 24, and 48 h.

Results:

Cell migration decreased after CSE exposure from both CCs and HTPs. At each time-point with 2.5% CSE, cell migration in the HTP group was less than that of the CC group. There were significant differences between the 2.5% CC and 2.5% HTP groups and the 5% CC and 5% HTP groups after 24 h. HTPs and CCs had similar effects in the wound-healing assay.

Conclusion:

Therefore, HTP use may be a risk factor for poor dental implant healing.
Collodion baby with ectropion in a Syrian newborn: a case report study
Authors: Soqia Jameel , Mohamad Lama , Aloqla Nizaar Adnan , Al Mouallem MHD Moamen , EID Mohammed Nader
Published: April 2023

Introduction and importance:

Collodion baby is a rare congenital disorder and a very intense disorder in which the baby suffers from several complications, such as trans-epidermal water loss. Only ∼270 cases of collodion babies have been reported in the literature since 1892. This disease may later develop one of a spectrum of diseases including lamellar ichthyosis, which the patient may had Congenital lamellar ichthyosis with ectropion, which was clinically distinguished by the collodion baby phenotype at birth.

Case presentation:

The authors are reporting the first case in Syria, a 20-day-old white Syrian male newborn, vaginally delivered at 38 weeks of pregnancy, with normal conditions, and congenital lamellar ichthyosis was shown by physical examination, as parchment-like scales were covering the newborn’s skin, which was starting to detach and showing the “collodion baby” appearance. Ophthalmologic examination revealed a bilateral ectropion of the upper eyelids with tarsal eversion. A treatment of Tobramycin 0.3% eye ointment was prescribed four times a day, with a viscotears liquid gel eye drops 4 times a day, and vaseline petroleum jelly to be applied three times daily. At 2-month follow-up, a significant improvement was noted.

Conclusion:

Ichthyosis have a wide range of disorders that involve the skin and have inherited and acquired forms. As a result, keratolytic and systemic retinoids can have significant benefits in restoring skin function.
Point-of-care ultrasound training in low-income countries: a need of time
Authors: Ali Noman , Soomar Salman M. , Waheed Shahan
Published: April 2023

Point of care ultrasound (POCUS) is “an ultrasonography performed at the bedside in real-time by the treating physician.” It is a powerful imaging modality used as an adjunct to physical examination and has gained momentum to become the future stethoscope. By using POCUS, the treating physician performs all image acquisition and interpretation and uses the information immediately to address specific hypotheses and guide the ongoing therapy. There is a shred of solid evidence that POCUS improves the diagnosis and management of acutely unwell patients is expanding rapidly. Due to the rise in the practice of POCUS in clinical medicine, the use of consultative ultrasonographic services has been reduced. The widespread availability of portable ultrasound machines and training an adequate number of clinicians to become competent in performing POCUS is a great challenge. The development of effective competency levels, curriculum, and assessment methods is imperative for the training of POCUS.
The rate and management of prosthetic joint infection in the low-income setting: a cross-sectional study
Authors: Hafez Mahmoud A. , Zamel Fouad , El-Khadrawi Tarek , El Ganzoury Ibrahim , Lotfy Abdel M. , Fansa Maher , Makram Abdelrahman M.
Published: April 2023

Introduction:

Although the rate of prosthetic joint infection (PJI) after total hip and knee arthroplasties (THA and TKA, respectively) is well documented in developed countries, there is a paucity of information in the literature on infection rates in low-and-middle-income countries. This study aims to review the PJI rate and management based on the Egyptian Community Arthroplasty Registry (ECAR) and six arthroplasty surgeons.

Methods:

Using data from the ECAR, for over 10 years, and surveying six high-volume arthroplasty surgeons, we reviewed the infection rate, common organisms, antibiotics used, and how the revision surgeries were done. The total number of patients included in this study was 210 infection cases out of 5216 THA and TKA.

Results:

Out of the 5216 joint replacement surgeries, the rate of all infections in THA and TKA was 4.03% (4.73 and 2.94%, respectively). The rate of infections requiring staged revision surgeries was 2.24 and 1.71% (2.03% in total) in the THA and TKA groups, respectively. The most encountered organism was Staphylococcus aureus. The common antibiotics used were vancomycin and a combination of cefoperazone and sulbactam.

Conclusion:

From this study, we conclude that THA was associated with a higher rate of PJI, surgeons’ use of antibiotics for a relatively long period, and the rate of PJI in our setting is relatively higher than what is reported in developed countries but lower in other low-income settings. We believe that with improved operating theater design and infection control education, infection rates will decrease significantly. Finally, we acknowledge the need for a national arthroplasty registry that can help in documentation and improving patient outcomes.
Metallic foreign bodies ingestion by schizophrenic patient: a case report
Authors: Jin Shengjian , Horiguchi Taigo , Ma Xiaolong , Yuan Shichao , Liu Qingguo
Published: April 2023

Introduction and Importance:

The ingestion of foreign objects is a widespread health issue, with a higher occurrence in adults with psychosis.

Case Presentation:

The authors present the case of a 39-year-old man who arrived at the hospital with symptoms of abdominal distension and occasional black stools for a week. The patient was known to have schizophrenia but had not received regular hospital follow-up or treatment for the past 5 years. He had a history of exogenous stimulation, which led him to surreptitiously swallow metallic objects. Upon physical examination, he displayed abdominal distension and mild tenderness in the upper abdomen. Radiographs revealed multiple foreign objects in his stomach, leading to the decision for laparotomy, gastric opening, and removal of the foreign objects under general anesthesia.

Clinical Discussion:

Mental illnesses, including schizophrenia, bipolar disorder, major depression, and multiple substance abuse, are recognized as being significant risk factors for ingesting foreign bodies. In such cases, it is crucial to intervene quickly. For patients presenting with psychiatric symptoms, the involvement of family caregivers is of even greater importance than endoscopic or surgical treatments.

Conclusion:

Foreign body ingestion is more prevalent in individuals with psychosis, highlighting the importance of ongoing care and follow-up for patients with mental illness.
Measles pneumonitis, an important cause to recognize in the era of COVID-19: a case report
Authors: Alawad Mouhammad J. , Nauman Areej , Ahmed Farheen S. , Kaul Ridhima , Neffati Nedia
Published: April 2023

Introduction and Importance:

Measles is an acute febrile viral illness with a characteristic rash. It is usually present in children. Due to the vaccine’s development and wide use, serious complications are quite infrequent in vaccine-covered areas.

Case Presentation:

A 36-year-old immunocompetent woman presented with a fever and a macular rash affecting the face and upper trunk. She was found to have transaminitis and later developed bilateral pulmonary infiltrates with decreased oxygen saturation. After extensive work, the measles PCR returned positive results. The patient was treated conservatively until she recovered.

Discussion:

Measles pneumonitis is a rare complication that usually occurs in immunosuppressed patients. Due to the coronavirus disease pandemic, diagnosis can be difficult, especially if the presentation is not classic.

Conclusion:

We report this case to emphasize the importance of correct diagnosis and proper management.
Displaced varus proximal humerus fracture with conservative treatment: a case report
Authors: Asavanapakas Panpaporn , Klabklay Prapakorn , Maliwankul Korakot , Chuaychoosakoon Chaiwat
Published: April 2023

Introduction and importance:

The authors report a case of an elderly female with a displaced varus misalignment of a proximal humerus fracture which met the indications for surgery, but the patient was treated conservatively with an arm sling due to the wishes of the patient and her relatives. The clinical outcome was nearly full function compared with the right shoulder.

Presentation of case:

A 65-year-old Thai female presented with right shoulder pain 1 h after a fall during which her right shoulder hit the floor. Radiographs of the right shoulder in anteroposterior and lateral transcapular views showed a proximal humerus fracture with varus misalignment. The patient and her relatives decided on conservative treatment with an arm sling. At 12 weeks following the fall she was able to move her right shoulder nearly equally to the left shoulder.

Intervention and outcome:

The authors discussed the treatment options with the patient and her relatives and recommended open reduction and internal fixation with a locking plate and screw, but they decided on conservative treatment with an arm sling. At 12 weeks following the fall she was able to move her right shoulder nearly equally to the left shoulder. She had no pain and could do normal life activities with the right shoulder.

Relevance and impact:

Patients with severe varus deformity are usually treated with surgery. If there are contraindications for surgery, the stability of the fracture should first be evaluated through radiographs of the fracture in various arm positions.
Kidney stone management in the era of miniaturized percutaneous nephrolithotomy: does it improve safety? a prospective cohort study
Authors: Sakly Aymen , Zakhama Walid , Jleli Nejm , Chafik Anas , Binous Yassine
Published: April 2023

Objective:

to compare the safety and the efficacy of standard percutaneous nephrolithotomy (sPCNL) vs. mini PCNL (mPCNL).

Methods:

The authors conducted a prospective single-centre cohort study over a 2-year period of all consecutive patients who underwent sPCNL or mPCNL for 2–4 cm renal stones. Patients with active urinary tract infection, abnormal coagulopathy state, malformative uropathies and multitract-access procedures were excluded. In total, 90 patients underwent sPCNL using a 30 Fr access sheath with 24 Fr nephroscope while 52 patients underwent mPCNL using a mPCNL system: 12 Fr nephroscope and a 16.5/17.5F access sheath. Blood loss estimation was assessed postoperatively after 6 h by considering haemoglobin drop and blood transfusion if required. Stone free rate at 1 month was defined by the absence of stone or residual fragments less than or equal to 3 mm on computed tomography scan.

Results:

Stone characteristics were comparable in both treatment arms. The mean stone size was comparable for sPCNL and mPCNL groups (32.6±10.8 mm vs. 29.4±11.8 mm). Operative time was longer in the mPCNL group (124±40.4 min vs. 95.8±32.3 min, P<0.001). According to the Clavien–Dindo classification, no statistical difference was found between the groups in terms of complication rate (P=0.092). However, the mean of haemoglobin drop and transfusion rate were significantly in favour of mPCNL (1.43±1.5 vs. 0.88±1.4 g/dcl, P=0.04). Hospital stay was found to be significantly shorter for patients undergoing mPCNL (4.4±3.9 vs. 2.7±1.7 days, P<0.001). The success rate in the sPCNL group was higher than mPCNL group in terms of stone clearance at one month (69.4% vs. 62.7%, P=0.06).

Conclusion:

Both sPCNL and mPCNL have shown good outcomes in this indication. Although the stone free rate was equal for both techniques, hospital stay, bleeding and transfusion rate are much lower with the use of mPCNL.
Descriptive Analysis of Newly Hired Academic Nurse Educator Onboarding Practices
Authors: Hansbrough Wendy , Dunker Kimberly , Duprey Melissa , Lawrence April
Published: April 2023

Background:

Prelicensure nursing programs often hire clinical experts who are novice educators to teach integration of nursing clinical judgment within the context of patient care experiences.

Purpose:

To describe practices of schools of nursing to onboard, orient, and mentor newly hired faculty.

Methods:

Faculty (n = 174) and leaders (n = 51) replied to an online survey.

Results:

The majority (81.63%) of leaders hire novice nurse educators; 58.14% require a minimum bachelor of science in nursing degree; 54.72% have an orientation plan consisting of a mean of 13.86 hours, which was mostly asynchronous learning. Of the 77.08% of leaders with an onboarding plan, 84.13% assign a preceptor; 51.35% of them are compensated.

Conclusions:

Most schools of nursing hire experienced clinical nurses who are novice nurse educators, without organizational structures to support acquisition of teaching expertise. Academic institutions are called on to support clinical nurse educator professional development. Evidence is needed to design effective and fiscally pragmatic onboarding programs based on the certified nurse educator competencies.
A Comparative Evaluation of Iliac Crest Cortical-Cancellous Bone Blocks Graft With and Without Concentrated Growth Factors (CGFs) in Secondary Alveolar Bone Grafting: A Retrospective Study
Authors: Lai Yongzhen , Jiang Xiao xian , Lu Meng , Mao Chuanqing , Cai Zhiyu , Wang Chengyong , Liu Jing , Chen Weihui
Published: April 2023

Background:

The purpose of this study was to investigate the clinical effect and bone resorption of iliac crest cortical-cancellous bone block grafts combined with concentrated growth factor (CGF) compared with iliac crest cortical-cancellous bone block grafts only in secondary alveolar bone grafting.

Materials and Methods:

Eighty-six patients (43 in the CGF group and 43 in the non-CGF group) with unilateral alveolar clefts were examined. Patients (17 in the CGF group and 17 in the non-CGF group) were randomly chosen for radiologic evaluation. Quantitative evaluation of the bone resorption rate was made with cone-beam computed tomography and Mimics 19.0 software at 1 week and 12 months after surgery.

Results:

The success rate of bone grafting was 95.3% and 79.1% in the CGF and non-CGF groups, respectively (P=0.025). The mean bone resorption rate at 12 months postoperatively was 35.66±15.80% and 41.39±19.57% in the CGF and non-CGF groups, respectively (P=0.355). The bone resorption patterns of the 2 groups were similar on the labial, alveolar process, and palatal sides, and there was no obvious bone resorption on the labial side in either group. Nasal side bone resorption in the CGF group was significantly less than that in the non-CGF group (P=0.047).

Conclusions:

Cortical-cancellous bone block grafts reduce labial bone resorption, while CGF reduces nasal bone resorption and improves the success rate. The combination of bone block and CGF in secondary alveolar bone grafting is worthy of further clinical application.
Abnormal degree centrality can be a potential imaging biomarker in first-episode, drug-naive bipolar mania
Authors: Li Guangyu , Zhang Baoli , Long Meixin , Ma Jun
Published: April 2023

Brain network abnormalities in emotional response exist in bipolar mania. However, few studies have been published on network degree centrality of first-episode, drug-naive bipolar mania, and healthy controls. This study aimed to assess the utility of neural activity values analyzed via degree centrality methods. Sixty-six first-episode, drug-naive patients with bipolar mania and 60 healthy controls participated in resting-state functional magnetic resonance rescanning and scale estimating. The degree centrality and receiver operating characteristic (ROC) curve methods were used for an analysis of the imaging data. Relative to healthy controls, first-episode bipolar mania patients displayed increased degree centrality values in the left middle occipital gyrus, precentral gyrus, supplementary motor area, Precuneus, and decreased degree centrality values in the left parahippocampal gyrus, right insula and superior frontal gyrus, medial. ROC results exhibited degree centrality values in the left parahippocampal gyrus that could distinguish first-episode bipolar mania patients from healthy controls with 0.8404 for AUC. Support vector machine results showed that reductions in degree centrality values in the left parahippocampal gyrus can be used to effectively differentiate between bipolar disorder patients and healthy controls with respective accuracy, sensitivity, and specificity values of 83.33%, 85.51%, and 88.41%. Increased activity in the left parahippocampal gyrus may be a distinctive neurobiological feature of first-episode, drug-naive bipolar mania. Degree centrality values in the left parahippocampal gyrus might be served as a potential neuroimaging biomarker to discriminate first-episode, drug-naive bipolar mania patients from healthy controls.
A tractable physical model for the yeast polarity predicts epistasis and fitness
Authors: Daalman Werner Karl-Gustav , Sweep Els , Laan Liedewij
Published: April 2023

Accurate phenotype prediction based on genetic information has numerous societal applications, such as crop design or cellular factories. Epistasis, when biological components interact, complicates modelling phenotypes from genotypes. Here we show an approach to mitigate this complication for polarity establishment in budding yeast, where mechanistic information is abundant. We coarse-grain molecular interactions into a so-called mesotype, which we combine with gene expression noise into a physical cell cycle model. First, we show with computer simulations that the mesotype allows validation of the most current biochemical polarity models by quantitatively matching doubling times. Second, the mesotype elucidates epistasis emergence as exemplified by evaluating the predicted mutational effect of key polarity protein Bem1p when combined with known interactors or under different growth conditions. This example also illustrates how unlikely evolutionary trajectories can become more accessible. The tractability of our biophysically justifiable approach inspires a road-map towards bottom-up modelling complementary to statistical inferences.

This article is part of the theme issue ‘Interdisciplinary approaches to predicting evolutionary biology’.
How predictable is adaptation from standing genetic variation? Experimental evolution in
Drosophila
highlights the central role of redundancy and linkage disequilibrium
Authors: Schlötterer Christian
Published: April 2023

Experimental evolution is well-suited to test the predictability of evolution without the confounding effects of inaccurate forecasts about future environments. Most of the literature about parallel (and thus predictable) evolution has been carried out in asexual microorganisms, which adapt by de novo mutations. Nevertheless, parallel evolution has also been studied in sexual species at the genomic level. Here, I review the evidence for parallel evolution in
Drosophila
, the best-studied obligatory outcrossing model for adaptation from standing genetic variation in the laboratory. Similar to asexual microorganisms, evidence for parallel evolution varies between the focal hierarchical levels. Selected phenotypes consistently respond in a very predicable way, but the underlying allele frequency changes are much less predictable. The most important insight is that the predictability of the genomic selection response for polygenic traits depends highly on the founder population and to a much lesser extent on the selection regime. This implies that predicting adaptive genomic response is challenging and requires a good understanding of the adaptive architecture (including linkage disequilibrium) in the ancestral populations.

This article is part of the theme issue ‘Interdisciplinary approaches to predicting evolutionary biology’.
Global epistasis on fitness landscapes
Authors: Diaz-Colunga Juan , Skwara Abigail , Gowda Karna , Diaz-Uriarte Ramon , Tikhonov Mikhail , Bajic Djordje , Sanchez Alvaro
Published: April 2023

Epistatic interactions between mutations add substantial complexity to adaptive landscapes and are often thought of as detrimental to our ability to predict evolution. Yet, patterns of global epistasis, in which the fitness effect of a mutation is well-predicted by the fitness of its genetic background, may actually be of help in our efforts to reconstruct fitness landscapes and infer adaptive trajectories. Microscopic interactions between mutations, or inherent nonlinearities in the fitness landscape, may cause global epistasis patterns to emerge. In this brief review, we provide a succinct overview of recent work about global epistasis, with an emphasis on building intuition about why it is often observed. To this end, we reconcile simple geometric reasoning with recent mathematical analyses, using these to explain why different mutations in an empirical landscape may exhibit different global epistasis patterns—ranging from diminishing to increasing returns. Finally, we highlight open questions and research directions.

This article is part of the theme issue ‘Interdisciplinary approaches to predicting evolutionary biology’.
Mutation bias and the predictability of evolution
Authors: Cano Alejandro V. , Gitschlag Bryan L. , Rozhoňová Hana , Stoltzfus Arlin , McCandlish David M. , Payne Joshua L.
Published: April 2023

Predicting evolutionary outcomes is an important research goal in a diversity of contexts. The focus of evolutionary forecasting is usually on adaptive processes, and efforts to improve prediction typically focus on selection. However, adaptive processes often rely on new mutations, which can be strongly influenced by predictable biases in mutation. Here, we provide an overview of existing theory and evidence for such mutation-biased adaptation and consider the implications of these results for the problem of prediction, in regard to topics such as the evolution of infectious diseases, resistance to biochemical agents, as well as cancer and other kinds of somatic evolution. We argue that empirical knowledge of mutational biases is likely to improve in the near future, and that this knowledge is readily applicable to the challenges of short-term prediction.

This article is part of the theme issue ‘Interdisciplinary approaches to predicting evolutionary biology’.
Alcanivorax xiamenensis sp. nov., a novel marine hydrocarbonoclastic bacterium isolated from surface seawater
Authors: Lai Qiliang , Fu Xiaoteng , Wang Jianning , Dong Chunming , Wang Liping , Wang Wanpeng , Shao Zongze
Published: April 2023

A novel

Alcanivorax

-related strain, designated 6-D-6T, was isolated from the surface seawater collected around Xiamen Island. The novel strain is Gram-stain-negative, rod-shaped and motile, and grows at 10–45 °C, pH 6.0–9.0 and in the presence of 0.5–15.0 % (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that it belongs to the genus

Alcanivorax

, with the highest sequence similarity to

Alcanivorax dieselolei

B5T (99.9 %), followed by

Alcanivorax xenomutans

JC109T (99.5 %),

Alcanivorax balearicus

MACL04T (99.3 %) and other 13 species of the genus

Alcanivorax

(93.8 %–95.6 %). The digital DNA–DNA hybridization and average nucleotide identity values between strain 6-D-6T and three close type strains were 40.1–42.9/90.6–91.4 %, and others were below 22.9/85.1 %, respectively. The novel strain contained major cellular fatty acids of C16 : 0 (31.0 %), C19 : 0
 ω8c cyclo (23.5 %), C17 : 0 cyclo (9.7 %), C12 : 0 3OH (8.6 %), summed feature 8 (7.6 %) and C12 : 0 (5.4 %). The genomic G+C content of strain 6-D-6T was 61.38 %. Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two unidentified phospholipids and one amino-group-containing phospholipid were detected. On the basis of phenotypic and genotypic characteristics, strain 6-D-6T represents a novel species within the genus

Alcanivorax

, for which the name Alcanivorax xiamenensis sp. nov. is proposed. The type strain is 6-D-6T (=MCCC 1A01359T=KCTC 92480T).
Single nuclei multiomic analyses identify human cardiac lymphatic endothelial cells associated with coronary arteries in the epicardium
Authors: Travisano Stanislao Igor , Harrison Michael R M , Thornton Matthew E. , Grubbs Brendan H. , Quertermous Thomas , Lien Ching-Ling
Published: April 2023

Cardiac lymphatic vessels play important roles in fluid homeostasis, inflammation, disease, and regeneration of the heart. The developing cardiac lymphatics in human fetal hearts are closely associated with coronary arteries, similar to those in zebrafish hearts. We identified a population of cardiac lymphatic endothelial cells that reside in the epicardium. Single nuclei multiomic analysis of the human fetal heart revealed the plasticity and heterogeneity of the cardiac endothelium. Furthermore, we found that VEGFC is highly expressed in arterial endothelial cells, providing a molecular basis for the arterial association of cardiac lymphatic development. Using a cell-type-specific integrative analysis, we identified a novel population of cardiac lymphatic endothelial cells marked by the PROX1, the lymphangiocrine RELN, and enriched in binding motifs of ETV transcriptional factors. We report the first in vivo molecular characterization of human cardiac lymphatics and provide a valuable resource to understand fetal heart development.
Retention time and fragmentation predictors increase confidence in variant peptide identification
Authors: Skiadopoulou Dafni , Vašíček Jakub , Kuznetsova Ksenia , Käll Lukas , Vaudel Marc
Published: April 2023

Precision medicine focuses on adapting care to the individual profile of patients, e.g. accounting for their unique genetic makeup. Being able to account for the effect of genetic variation on the proteome holds great promises towards this goal. However, identifying the protein products of genetic variation using mass spectrometry has proven very challenging. Here we show that the identification of variant peptides can be improved by the integration of retention time and fragmentation predictors into a unified proteogenomic pipeline. By combining these intrinsic peptide characteristics using the search-engine post-processor Percolator, we demonstrate improved discrimination power between correct and incorrect peptide-spectrum matches. Our results demonstrate that the drop in performance that is induced when expanding a protein sequence database can be compensated, and hence enabling efficient identification of genetic variation products in proteomics data. We anticipate that this enhancement of proteogenomic pipelines can provide a more refined picture of the unique proteome of patients, and thereby contribute to improving patient care.
Role of pioneer neurons and neuroblast behaviors on otic ganglion assembly
Authors: Bañón A , Alsina B
Published: April 2023

Cranial ganglia are aggregates of sensory neurons that mediate distinct types of sensation. It is little understood how individual neurons coalesce, distribute and shape the ganglion. The statoacoustic ganglion (SAG) displays several lobes spatially arranged to properly connect with hair cells of the inner ear. To investigate the cellular behaviors involved in the 3D organization of the SAG, we use high resolution confocal imaging of single cell labeled zebrafish neuroblasts (NB), photoconversion, photoablation and genetic perturbations. We find that otic NB delaminate out of the otic epithelium in an EMT-like manner, rearranging apical polarity and primary cilia proteins. We also show that, once delaminated, NB migrate directionally and actively, requiring RhoGTPases. Interestingly, cell tracking of individual delaminated NB reveals that NB migrate and coalesce around a small population of pioneer SAG neurons. These pioneer SAG neurons are not from otic placode origin and populate the coalescence region before otic neurogenesis begins. Upon ablation of these cells, migratory pathways of delaminated NB are disrupted and, consequently, SAG shape is affected. Altogether, this work shows for the first time the role of pioneer SAG neurons in orchestrating SAG development.

Summary Statement

Little is known how cranial sensory ganglia organize in 3D. We unveil the repertoire of cellular behaviours underlying statoacoustic morphogenesis and its dependence on relevant pioneer neurons.
Microtomographic investigation of a large corpus of cichlids
Authors: Haberthür David , Law Mikki , Ford Kassandra , Häsler Marcel , Seehausen Ole , Hlushchuk Ruslan
Published: April 2023

A large collection of cichlids (N=133) from Lake Victoria in Africa spanning a length range of 6 to 18 cm was nondestructively imaged using micro-computed tomography. We describe our method to efficiently obtain three-dimensional tomographic datasets of the oral and pharyngeal jaws and the whole skull of these fishes for accurately describing their morphology. The tomographic data we acquired (9.8 TB of projection images) yielded 1.5 TB of three-dimensional image stacks used for extracting the relevant features of interest. Herein we present our method and an outlook on analyzing the acquired data; a morphological description of the oral and pharyngeal jaws of the fishes, a three-dimensional geometric morphometrics analysis of landmark features on the fish skulls, and a robust method to automatically extract the otoliths of the fishes from the tomographic data.
PanGraphViewer: A Versatile Tool to Visualize Pangenome Graphs
Authors: Yuan Yuxuan , Ma Ricky Ka-Kui , Chan Ting-Fung
Published: April 2023

Pangenome graphs provide a powerful way to present both sequence and structural features in a given genome relative to the typical features of a population. There are different methods of building pangenome graphs, but few tools are available to visualize them. To address this problem, we developed PanGraphViewer, which is written in Python 3 and runs on all major operating systems. The PanGraphViewer package contains two separate versions: a desktop-based application and a web-based application. Compared to other graph viewers that are initially designed to visualize individual genome graphs, PanGraphViewer targets pangenome graphs and allows the viewing of pangenome graphs built from multiple genomes in either the (reference) graphical fragment assembly format or the variant call format (VCF). Apart from visualization of different types of structural variations (SV), PanGraphViewer also integrates genome annotations with graph nodes to analyze insertions or deletions in a particular gene model. The graph node shapes in PanGraphViewer can represent different types of genomic variations when a VCF file is used. Notably, PanGraphViewer displays subgraphs from a chromosome or sequence segment based on any given coordinates. This function is absent from most genome graph viewers. PanGraphViewer is freely available athttps://github.com/TF-Chan-Lab/panGraphViewerto facilitate pangenome analysis.
Cell-derived ECM loaded electrospun Polycaprolactone/Chitosan nanofibrous scaffolds for periodontal regeneration
Authors: Santos Mafalda S. , Cordeiro Rachel , Moura Carla S. , Cabral Joaquim M. S. , Ferreira Frederico Castelo , Silva João C. , Carvalho Marta S.
Published: April 2023

Periodontitis is an inflammatory infection caused by bacterial plaque accumulation that affects the periodontium, a complex structure of different tissues (cementum, periodontal ligament and alveolar bone) that surrounds and supports the teeth. Current treatments lack bioactive signals to induce tissue repair and coordinated regeneration of the periodontium, thus alternative strategies are needed to improve clinical outcomes. Cell-derived extracellular matrix (ECM) has been combined with biomaterials to enhance their biofunctionality for various tissue engineering (TE) applications. In this work, bioactive cell-derived ECM loaded electrospun polycaprolactone/chitosan (PCL/CTS) nanofibrous scaffolds were developed combining polymer solutions with lyophilized decellularized ECM (dECM) derived from human Periodontal Ligament Stem/Stromal Cells (PDLSCs). The work’s aims were to fabricate and characterize cell-derived ECM electrospun PCL/CTS scaffolds in terms of morphology, physico-chemical, thermal and mechanical properties and assess their ability to enhance the osteogenic differentiation of PDLSCs, envisaging periodontal TE applications. PDLSCs were cultured and used for dECM production. PDLSCs-derived dECM was characterized regarding morphology, protein expression, DNA removal efficiency, and glycosaminoglycans and collagen contents. Osteogenic differentiation of PDLSCs was performed on PCL, PCL/CTS and PCL/CTS/ECM electrospun scaffolds for 21 days. The obtained results demonstrate that PCL/CTS/ECM scaffolds promoted cell proliferation compared to PCL and PCL/CTS scaffolds, while maintaining similar physical and mechanical properties of PCL/CTS scaffolds. PCL/CTS/ECM scaffolds enhanced the osteogenic differentiation of PDLSCs, confirmed by increased alkaline phosphatase activity, calcium deposition, and bone-specific marker genes expression. Moreover, PCL/CTS scaffolds showed higher levels of cell mineralization than PCL scaffolds. Overall, this work describes the first use of lyophilized cell-derived ECM loaded electrospun scaffolds for periodontal TE applications and highlights its potential as a promising therapeutic strategy for periodontitis treatment.
CRD: aDe novoDesign algorithm for prediction of Cognate Protein Receptors for small molecule ligands
Authors: Sankar Santhosh , Chandra Nagasuma
Published: April 2023

While predicting a new ligand to bind to a protein is possible with current methods, the converse of predicting a receptor for a ligand is highly challenging, except for very closely-related known protein-ligand complexes. Predicting a receptor for any given ligand will be path-breaking in understanding protein function, mapping sequence-structure-function relationships and for several aspects of drug discovery including studying the mechanism of action of phenotypically discovered drugs, off-target effects and drug repurposing. We use a novel approach for predicting receptors for a given ligand throughde novodesign combined with structural bioinformatics. We have developed a new algorithm CRD, that has multiple modules which combines fragment-based sub-site finding, a machine learning function to estimate the size of the site, a genetic algorithm that encodes knowledge on protein structures and a physics-based fitness scoring scheme. CRD has a pseudo-receptor design component followed by a mapping component to identify possible proteins that house the site. CRD is designed to cater to ligands with known and unknown complexes. CRD accurately recovers sites and receptors for several known natural ligands including ATP, SAM, Glucose and FAD. It designs similar sites for similar ligands, yet to some extent distinguishes between closely related ligands. More importantly CRD correctly predicts receptor classes for several drugs such as penicillins and NSAIDs. We expect CRD to be a valuable tool in fundamental biology research as well as in the drug discovery and biotechnology industry.