bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical Pharmacology of Ziprasidone (Geodon® or Zeldox®) From the Food and Drug Administration (FDA) Reviewer
Authors: Habet Sam
Published: March 2022

Ziprasidone (Geodon®), also known at the time of submission to the Food
and Drug Administration (FDA) as Zeldox®. It was submitted initially for
the treatment of psychiatric disorders e.g., Schizophrenia. However,
there was delay on its approval due to increase of QT prolongation,
which was discussed at the FDA Advisory Committee. This review focused
on the clinical pharmacology and the pharmacokinetics (PK) of the drug,
specifically at the time of submission to the FDA and other related
updated references. The sponsor (Pfizer) summitted about 40 clinical
pharmacology and PK studies including QT prolongation studies. There
were four capsules formulation at that time: 20, 40, 60, and 80 mg and
one intramuscular (IM) strength in another New Drug Administration (NDA)
that came subsequent to oral route. The drug has to be given with food
to increase the bioavailability to 60% (two-fold increase). Ziprasidone
is extensively metabolized after oral administration with only a small
amount excreted in the urine (<1%) or feces (<4%)
as unchanged drug. Approximately 20% of the dose is excreted in the
urine, with approximately 66% being eliminated in the feces. Some of
its metabolites are active. Ziprasidone has very high, sub nanomolar
binding affinity for the human serotonin.
Aort the pearl, incidentally detected aortitis during coronary bypass surgery: A case report
Authors: Buğra Abdul Kerim , Buğra Aytul , Kadirogullari Ersin , Onan Burak
Published: March 2022

Aortitis, in its simplest definition, is an inflammation of the aorta.
It can be divided into two groups as infectious and non-infectious.
Noninfectious aortitis can be an involvement of multisystemic and
autoimmune diseases as well as being diagnosed incidentally. In our
case, in which we planned elective coronary bypass surgery, we
encountered an ascending aorta with a pearlish color, dilated and firm
consistency intraoperatively. Histopathological examination showed
extensive lymphoplasmocytic infiltration and strotiform fibrosis. In the
laboratory tests performed for etiology in the postoperative period, no
abnormalities were observed in the early and long term. Even when
detected isolated and incidentally, aortitis may be a component of a
multisystemic and/or autoimmune disease. The time of diagnosis may
coincide with the asymptomatic period of the systemic disease. We wanted
to present this case because it was detected incidentally during
coronary bypass surgery and was diagnosed histopathologically
immunoglobulin-G4 related aortitis, although it was not found in
clinical and laboratory evaluations.
Ovomucoid-specific IgD increases in children who naturally outgrow egg allergy
Authors: Itoh Naohiro , Yasutomi Motoko , Kawasaki Akiko , Murai Hiroki , Nomura Eishi , Hagihara Yuuki , Ogura Kazumasa , Ohshima Yusei
Published: March 2022

Background: The majority of egg-allergic children outgrow
hypersensitivity against heated egg and then raw egg over time. The
roles of ovomucoid (OVM)- and ovalbumin (OVA)-specific IgD in children
who naturally outgrow egg allergy are uncertain. We investigated whether
specific IgD to egg white (EW), OVM, and OVA correlate with
allergen-specific IgE and can predict the development of immune
tolerance to egg allergens. Methods: The tolerated doses of cooked egg
white, which were determined by oral food challenge and/or an episode of
accidental ingestion and corresponding specific IgE, IgG4 and IgD levels
were evaluated in 57 children with egg allergy and 23 non-egg allergic
children. Results: Patients avoiding all forms of egg had lower EW-,
OVM-, and OVA-specific IgD and IgG4 than those partially avoiding egg,
those that had outgrown egg allergy, and non-egg allergic children. The
ratio of OVM-specific IgD to OVA-specific IgD increased depending on the
ingestible amounts of boiled EW, whereas the ratio of OVM-specific IgG4
to OVA-specific IgG4 did not change. Receiver operating curve analysis
revealed that the ratio of OVM-specific IgE to OVM-IgD was the best
index to discriminate intolerant from tolerant egg-allergic patients.
Conclusion: The production of OVM-specific IgD differs from OVM-specific
IgG4 as children naturally outgrow egg allergy. The ratio of
OVM-specific IgE to OVM-specific D is useful in distinguishing
egg-sensitized patients with clinically reactive egg allergy from those
who naturally outgrow egg allergy.
Association of Serum Surfactant Protein D and SFTPD gene variants with asthma in Danish children, adolescents and young adults
Authors: Hoffmann-Petersen Benjamin , Suffolk Raymond , Petersen Jens Jakob Herrche , Petersen Thomas Houmann , Brasch-Andersen Charlotte , Hoest Arne , Halken Susanne , Sorensen Grith Lykke , Agertoft Lone
Published: March 2022

Background: Surfactant Protein D (SP-D) is a pattern recognition
molecule belonging to the collectin family expressed in multiple human
organ systems including the lungs. Previous studies have shown that SP-D
concentrations in bronchoalveolar lavage samples decreases and serum
concentrations increases in patients with asthma possibly attributable
to a combination of induced SP-D synthesis and decreased air-blood
barrier integrity. The aims of this study were to investigate if the
serum level of SP-D and common variations in the SP-D gene were
associated to asthma in adolescents and young adults. Methods:
Prospective observational study including 449 adolescents and young
adults (age 11-27 years) previously diagnosed with asthma during a
two-year period from 2003 to 2005 (0-16 years). At follow-up from 2016
to 2017 314 healthy controls with no medical history of asthma were
recruited. Serum SP-D was analyzed on samples obtained at baseline as
well as samples obtained at follow-up. SP-D genotyping was performed for
rs721917, rs2243639 and rs3088308. Results: No differences were found in
mean levels of sSP-D and SFTPD genotype among subjects with current
asthma, no current asthma and controls. Serum SP-D and SFTPD genotype
were not associated to any clinical parameters of asthma. Furthermore,
baseline sSP-D was not associated to asthma at follow-up. Conclusion:
Serum surfactant protein D and common SP-D gene variants were not
associated with asthma in Danish adolescents and young adults with mild
to moderate asthma. Serum surfactant protein D did not demonstrate any
value as a clinical biomarker of asthma.
Effect of redox atmosphere treatment on bifunctional Ga/ZSM-5 for efficient catalytic cracking of n-butane
Authors: Ni Zenan , Li Yuming , Zhang Yaoyuan , Wang Yajun , Cui Guoqing , Jiang Guiyuan , Zhao zhen , Xu Chunming
Published: March 2022

Ga species with high dehydrogenation capability were prepared by H2-O2
atmosphere treatment, and efficient matching of bifunctionality
(dehydrogenation/cracking) was realized between Ga species and ZSM-5
over Ga/ZSM-5 based catalysts. Compared with parent Ga/ZSM-5, the
conversion rate of n-butane was increased from 0.53 to 2.59
mmol·g-1·min-1 on Ga/ZSM-5 with H2-O2 treatment. Kinetic analysis
revealed that the apparent activation energy of n-butane catalytic
cracking decreased largely from 141 to 47 kJ·mol-1, which is attributed
to the formation of new interaction between Ga species and ZSM-5 upon
such an atmosphere treatment. It was also found butane-O2 treatment acts
as a similar role with H2-O2 treatment in enhancing the catalytic
performance. On this basis, different Ga species were correlated with
activity and kinetic data, and the effect of practical reaction
atmosphere on Ga species was also investigated.
Active Disturbance Rejection Thermal Control of a Mechanically Pumped Two-Phase Loop: An Experimental Study
Authors: Zhang Chengbin , Li Guanru , Sun Li , Chen Yongping
Published: March 2022

High-heat-flux heat removal is critical for the long-term safety of the
high-power electronic device, while the precise and uniform temperature
control is challenging due to various uncertainties. To this end, active
disturbance rejection controller (ADRC), hybrid with feed-forward
flow-rate/sub-cooling controller, is introduced for the temperature
regulation of a multiple degree-of-freedom mechanically pumped two-phase
loop. Based on the proposed experimental setup, the optimal references
of sub-cooling and flow-rate are identified and used as the feed-forward
law for auxiliary loop control, and ADRC is used in the primary loop to
control the evaporator wall temperature. The experimental results
indicate the efficiency of thermal control for the mechanically pumped
two-phase loop via combination of primary and auxiliary loop. In
addition, ADRC performs better in both temperature tracking and
disturbance rejection when compared with the conventional PI controller,
and its superiority consists in faster tracking and stronger robustness
to disturbances and couplings.
Synthesis of esomeprazole catalyzed by immobilized cells
Authors: zhang yuanyuan , Zhao Qiuxiang , Tang Hui , Li huiling , Li depeng , Wang zhiyong , Wang Fanye , Gao xin
Published: March 2022

The asymmetric sulfoxidation of the omeprazole thioether to synthesize
esomeprazole catalyzed by immobilized cells of a mutant of Rhodococcus
rhodochrous ATCC 4276 in the chloroform–water biphasic system was
carried out at a high substrate concentration (200mM) and optimized
using response surface methodology (RSM). The optimal yield of
esomeprazole obtained was 94.8% with e.e. (>99%) without
the formation of the sulfone. A quadratic polynomial model was developed
with R2 of 0.9998, which indicates that the model predicts the observed
data with very high accuracy. The mutant exhibited a high
enantioselective, activity and substrate and product tolerance. The
significant improvement of substrate tolerance may mainly be contributed
by employing the chloroform–water biphasic system because almost all
substrates may partitioned in the organic phase, resulting in little
damage and inhibition to cells by substrates.
NMDA Receptor Potentiation and Severe Acute Respiratory Syndrome Treatment
Authors: Costa Blaise
Published: March 2022

An experimental compound (CNS004), reported to have various biological
activities including antiviral, antimalarial, antiprotozoal and
immunomodulatory effects, has been identified to potentiate NMDA subtype
of glutamate receptors that are expressed in human lungs and central
nervous system. We hypothesize that potentiating NMDA receptors will
increase calcium ion influx and promote downstream signaling mechanisms
associated with cellular contractions which is disrupted in severe acute
respiratory syndrome. Pharmacological effects generated by triggering
central nervous system glutamate receptor function, coupled with
concurrent stimulation of the respiratory tract, may produce a
synergetic effect in improving the airway smooth muscle function.
Further, an antiviral activity combined with immunomodulatory effect of
this experimental compound may improve the symptoms of viral diseases.
This novel multipronged intervention to simultaneously inhibit viral
proteins and promote host cell functions would be helpful to develop
clinically useful compounds for the treatment of emerging viral diseases
that deteriorate peripheral and central nervous system function before
causing death in human beings.
IL-36α inhibits the progression of Colorectal Cancer via inhibit the ability of tumor cells and enhance the infiltration and function of CD8+ T lymphocyte cells
Authors: wei xiuyu , yao yongjie , wang xiaoxi , sun jiaxin , qiu lu , Zhao Wenshan , Zhai Wenjie , qi yuanming , Wu Yahong , gao yanfeng
Published: March 2022

Colorectal cancer (CRC) is the world’s third most deadly disease, it is
very urgent to discover new diagnostic biomarker and therapeutic
targets. Interleukin-36α (IL-36α) is a proinflammatory factor, which can
initiate the inflammatory response and especially raise the overall
systemic Th1 immune response. In the present study, we clarified the new
role of IL-36α in colorectal cancer. we observed that IL-36α is
down-regulated in human colorectal cancer tissues and colorectal cancer
patients with high IL-36α expression had a better prognosis. Then, we
constructed IL-36α overexpressing cell lines CT26-IL-36α and HT29-IL-36α
to verify the effect of IL-36α on tumor cells. Results showed that
IL-36α over-expression could directly inhibit the proliferation, the
migration and invasion of tumor cells. We then established CT26 and
CT26-IL-36α tumor xenograft model and lung metastasis model to determine
the effect of IL-36α in vivo. Results showed that IL-36α overexpression
could significantly inhibit the growth and lung metastasis of tumors,
and enhance the infiltration and cytokine secretion of CD8+ T lymphocyte
cells. Then, we found that CT26-IL-36α secrete more CXCL10 and CXCL11 to
enhance the infiltration of CD8+ T lymphocyte than that of CT26-vector
cells. These results suggested that IL-36α could serve as a promising
therapeutic target for colorectal cancer through directly inhibiting the
ability of tumor cells and enhancing the infiltration and function of
CD8+ T lymphocytes.
Protein-Protein interactions of human gut cell receptor α, β-3-integrin, and ErbB2 with SlpAKB290 homology model
Authors: Swamy Vyshanava Satyanarayana , Kumar Kanderi Dileep , Rao Dowlatabad Muralidhara
Published: March 2022

Surface layer protein, which is abundant in the gram-positive bacteria
like Lactobacillus sp, for its adherence and symbiotic activity in the
normal flora of gastrointestinal tracts. In this study, we showed the
relative binding of the SlpAKB290, a homology-based model with a higher
binding affinity to ErbB2 rather than the α, β-3integrin-binding domain
through molecular docking. The critical binding affinity had been
demonstrated with the protein-protein docked clusters’ flexibility and
rigidity through the normal mode simulations and thermal unfolding to
identify the constraint networks. The results showed a better
performance SlpAKB290 with the ErbB2. The current study provided
essential insight into the Lactobacilli sp.’s adherence to the host
cells through protein-protein interactions.
Food comes in bites: mammalian dietary space in terms of food items, nutrition and energy
Authors: Lintulaakso Kari , Tatti Nikolaj , Žliobaitė Indrė
Published: March 2022

This paper presents a new computationally derived reference framework of
mammalian dietary categories in terms of food items consumed and their
nutritional and energetic content. We analyse the diets of 82% of the
mammalian species alive today. The analysis describes four major dietary
specialisations in the nutritional spectrum — animalivores with
high-energy diets, herbivores and frugivores with medium-to-low energy
and in the middle of the space sparsely populated omnivores. This study
highlighting omnivory as a heterogeneous, medium energy concept with
often non-overlapping types of omnivory in the dietary space. We also
show that some of the commonly used categories, such as herbivore-grazer
and herbivore-mixed-feeder, even though distinct with regard to food
items, overlap very closely in nutritional space. Overall, we conclude
that while energetically food items make a continuum, in the nutritional
space they are clustered. Together, these ﬁndings imply that true
omnivory cannot be common.
Comparative proteomics combined with morphophysiological analysis revealed low temperature response mechanism in two contrasting maize genotypes
Authors: Zou Jinpeng , Yang Liang , Li Yuhong , Piao Mingxin , Li Jingdu , Li Yaxing , Yao Nan , Li Zhifang , Zhang Xiaohong , Zhang Qian , Hu Guanghui , Yang Deguang , Zuo Zecheng
Published: March 2022

Environmental conditions affect the growth and development of maize, and
low temperature has been widely concerned as one of the most important
factors. In the temperate zone, maize is found to be under chilling
stress in its growth and development, especially at the seedling stage.
Correspondingly, maize generates various measures to alleviate such
stress, and its regulation of protein expression is one of the most
effective. However, further research on the regulation mold has not yet
been carried out. To gain a better understanding of the regulation mold,
we used two inbred lines with different resistance, which are chilling
tolerant KR701 and chilling sensitive hei8834, to undergo quantitative
proteomics analysis under chilling stress at the one- and three-leaf
stages, respectively. The results revealed diversified cold-resistant
pathways of maize with different resistance at different stages of
seedling, and the reasons behind. Meanwhile, we found that ABA in
hormone response pathway plays an important role in improving the cold
resistance of maize at one-leaf stage, which lays a solid foundation for
further explorations of the cold-resistant mechanism in maize at the
seedling stage, and enlightens strategic improvements of the cold
resistance in world crops.
The wheel-shaped composite cartilage graft for type 1 tympanoplasty: Comparison with palisade and island cartilage graft.
Authors: Çiğer Ejder , İşlek Akif , Yazır Mustafa
Published: March 2022

Objectives: This study aims to compare the graft success and hearing
results of the palisade and island cartilage graft, with a new
wheel-shaped composite cartilage graft for type 1 tympanoplasty. Design:
The study was designed retrospectively. Setting: The study was conducted
at Katip Celebi University, Ataturk Training and Research Hospital,
Otolaryngology-Head & Neck Surgery Clinic. Participants: Only patients
with conductive hearing loss and simple pars tensa perforation of the
tympanic membrane were included in the study. Main outcome measures:
Pure tone average (PTA), air-bone gap gain (ABG), word recognition score
(WRS), ABG closure and grafts success were compared between the graft
groups. Results: Records of 111 patients were analyzed. The graft
success rate was 89.7% for palisade cartilage graft (PCG, n= 39),
86.1% for island cartilage graft (ICG, n=36), and 97.2% for
wheel-shaped composite cartilage graft (WsCCG, n= 36) (p=0.244). Average
postoperative PTA and ABG values were significantly affected by the
cartilage graft type, but WRS was not affected. (p = 0.005, 0.019,
0.306, respectively, One Way-Anova test). Post-Hoc LSD test showed a
statistically significant decrease in PTA and ABG averages for WsCCG
group compared to the ICG group (p= 0.004; CI%95= 15.1-2.2 dB and p=
0.023; CI%95= 8.2-0.4 dB, respectively). Postoperative PTA and ABG
averages for WsCCG and PCG groups were similar (p= 0.069 and p=0.053,
respectively). In addition, while there were 2 (5.1%) retractions in
the PCG group and 1 (2.7%)in the ICG group, there was no retraction in
the WsCCG group. Conclusion: The WsCCG provided comparable results with
classical reliable graft techniques (PCG and ICG) and may recommend as a
more suitable graft due to hearing results and resistance against
retraction.
Assessing long-term renal outcome after allogeneic hematopoietic stem cell transplantation in children with estimated glomerular filtration rate equations, based on creatinine and cystatin C levels.
Authors: Gadashova Aysha , Tunçay Seçil Conkar , Ozek Gülcihan , Hakverdi Gülden , Kansoy Savaş , Kabasakal Caner , Aksoylar Serap
Published: March 2022

Background: With the widespread use of hematopoietic stem cell
transplantation (HSCT), long-term complications have come to the fore.
The aim of this study is to determine the prevalence and risk factors of
chronic kidney disease (CKD) developing in the long term in patients who
underwent allogeneic HSCT in childhood and also to investigate the
superiority of eGFR formulas. Methods: The present study evaluated CKD
in patients undergoing allogeneic HSCT. We analyzed the 94 children who
received allogeneic HSCT at the Ege University in İzmir between 2019
August and 2019 November. The patients were evaluated at least 2 years
after transplantation. CKD was defined as a glomerular filtration rate
(GFR)<90 mL/min/1.73 m2, using eGFR equations which are based
on serum creatinine (SCr), cystatin C (CysC), and SCr plus CysC.
Results: In our study, 9 (9.4%) according to Bedside Schwartz, 59
(76.6%) according to CKiD-eGFR-CysC and 20 (26%) patients according to
CKiD-eGFR-SCr-CysC equation were evaluated as CKD. In cases evaluated as
CKD according to CysC, early development of acute kidney injury (AKI),
posttransplant cytomegalovirus (CMV) reactivation and being
>10 years old during transplantation were found to be
associated with the development of CKD. Conclusion: We may be delayed in
detecting CKD by calculating SCr-based formulas in HSCT cases, which is
a patient group where early diagnosis and treatment of CKD is very
important.
Weight Gain According to Pregnancy Period and Affecting Factors
Authors: küçük izzet , Eser Utku , Baser Duygu Ayhan , ÇEVİK MURAT , Öngel Kurtuluş , Seval Sevilay
Published: March 2022

Aims: The aim of the study was to investigate the effect of
pre-pregnancy body mass index on weight gain during pregnancy. Methods
and Material: This retrospective study was conducted on family medicine
units in Turkey between March 2018 to September 2018. Pregnant files of
the last 5 years were scanned and a questionnaire with 40 questions was
filled. Results: 1061 pregnants from 72 provinces included in the study.
Net weight difference during pregnancy was significantly higher in
cesarean patients, in civil servants and in those with first pregnancy
(p <0.05). Net weight difference was found to be significantly
lower in those without education compared to other groups (p
<0.05). Conclusions: Consequently, In conclusion,
pre-pregnancy BMI and individual weight gain during pregnancy should be
planned. Thus, many complications that may develop in mother and baby
can be prevented. In this regard, benefiting from family medicine units
that can reach all segments of the society and monitor pregnant women
can increase their success rates. Key-words: Pregnancy, body mass index,
gestational weight gain Key Messages: What’s already known about this
topic? • According to various studies, nearly half of today’s pregnant
women are overweight or obese • The body weight of the mother before
pregnancy and the weight gained during pregnancy have an effect on
pregnancy results. What does this article add? • Lifestyle changes
required for ideal BMI should be planned in pre-pregnancy counseling. To
achieve this, teams of family physicians, dieticians and individual
sports trainers should be formed. • Those in the high risk group (eg,
first pregnancy, uneducated and civil servant) should be monitored more
frequently in terms of weight gain during pregnancy. • Personal and
social information should be provided to correct false information that
taking iron and multivitamin support during pregnancy causes weight
gain.
Modified leak-proof puncture technique using a plastic wrap and instant cyanoacrylate glue for the resection of giant ovarian cyst at minilaparotomy
Authors: Ishikawa Hiroshi , Tanaka Hirokazu , Shozu Makio
Published: March 2022

We modified our leak-proof puncture technique for the aspiration of
giant ovarian cyst contents while strengthening the punctured cyst wall.
After making the minilaparotomy incision, we lined a sterile gauze with
the cyst surface, applied instant cyanoacrylate glue, and attached a
plastic wrap over a wound retractor. The adhesion side was reinforced by
the gauze and was difficult to split when aspirating the cyst contents.
We then drew the cyst outside the body and performed cystectomy or
oophorectomy under a narrow field of direct vision. This technique is
easy and cost effective for the resection of giant ovarian cystic
tumors.
Als3-Th-cell-epitope plus the combined adjuvant of MDP, CpG and FIA synergistically enhanced the immune responses triggered with recombinant TRAP proteins in mice
Authors: Ma Jinzhu , Liu Wei , Wang Beiyang , Yu Simiao , Yu Liquan , Song Baifen , Yu Yongzhong , Zhu Zhanbo , Cui Yudong
Published: March 2022

Here, Als3-Th-cell-epitope （Als3 epitope） was connected to the
N-terminal of TRAP by flexible linker, and the Als3-Th-cell-epitope-TRAP
(ATT) proteins were prepared, then, the ATT proteins plus freund’s
adjuvant were inoculated in mice to evaluate Als3 epitope to increase
the immunogenicity of TRAP. To strengthen the immunogenicity of ATT
protein, the proteins plus the novel combined adjuvants of MDP, CpG and
FIA were immunized in mice. After the booster immunization, the results
showed that the mice immunized with ATT protein plus Freund’s adjuvant
exhibited significantly higher level for IFN-γ, IL-4, IL-10 and IL-17A,
and displayed the stronger humoral immune response against TRAP than the
control groups, importantly, the survival rate of these mice was
significantly higher than the control groups. In addition, the mice
immunized with ATT protein plus CpG+MDP+FIA adjuvants exhibited
significantly higher level for IFN-γ and IL-17A than other groups, and
the level of IgG antibody against TRAP was higher than other groups,
moreover, the survival rate of these mice was obviously higher than
other groups. These data suggested that the immune protection triggered
with ATT was significantly stronger than TRAP or TRAP+Als3 epitope did,
which indicted Als3 epitope significantly enhanced the immune responses
triggered with TRAP through their fused forms of expression.
Additionally, these data manifested that ATT plus the novel combined
adjuvant, MDP, CpG and FIA, induced the strongest immune response and
protection against S.aureus among all the groups, revealing the
synergistic effect on different adjuvant. This study provides an
important reference for the further development of a new effective
vaccine against S.aureus.
PROTEIN FOLDING - SEEING IS DECEIVING
Authors: Rose George
Published: March 2022

This Perspective is intended to raise questions about the conventional
interpretation of protein folding. According to the conventional
interpretation, developed over many decades, a protein population can
visit a vast number of conformations under unfolding conditions, but a
single dominant native population emerges under folding conditions.
Accordingly, folding comes with a substantial loss of conformational
entropy. How is this price paid? The conventional answer is that
favorable interactions between and among the side chains can compensate
for entropy loss, and moreover, these interactions are responsible for
the structural particulars of the native conformation. Challenging this
interpretation, the Perspective introduces a proposal that high energy
(i.e., unfavorable) excluding interactions winnow the accessible
population substantially under physical-chemical conditions that favor
folding. Both steric clash and unsatisfied hydrogen bond donors and
acceptors are classified as excluding interactions, so called because
conformers with such disfavored interactions will be largely excluded
from the thermodynamic population. Both excluding interactions and
solvent factors that induce compactness are somewhat non-specific, yet
together they promote substantial chain organization. Moreover, proteins
are built on a backbone scaffold consisting of a-helices and strands of
b sheet, where the number of hydrogen bond donors and acceptors is
exactly balanced. These repetitive secondary structural elements are the
only two conformers that can be both completely hydrogen-bond satisfied
and extended indefinitely without encountering a steric clash. Putting
the “bottom line” at the top: it is likely that hydrogen-bond
satisfaction represents a largely overlooked parameter in protein
folding models.
Diagnostic value of serum tumor markers for epithelial ovarian cancer stage I-II -- A retrospective analysis
Authors: yi qiang , ran yu , Li Cong
Published: March 2022

Objective epithelial ovarian cancer (EOC) in early stage is difficult to
diagnose. Serum indicators for stage I-II of epithelial ovarian cancer
which confined to pelvic cavity were found through retrospective
analysis, possible early detection methods might be found. Methods 165
patients were diagnosed as epithelial ovarian cancer at stage I-II from
January 1st, 2015 to December 31st, 2019. Data was collected including
age, pathological type, serum D-dimer (D-D), neutrophil to lymphocyte
ratio (N/L), the platelet to lymphocyte ratio (P/L), cancer antigen 125
(CA125), human epididymis protein 4 (HE4) and diameter of the ovarian
mass by ultrasound. Result D-D, CA125, HE4, ROMA, diameter, pathological
type and age were significantly different in the different stage, age
showed independent effect after logistical regression (P <
0.05). D-D, CA125, HE4, ROMA, diameter, age and stage were significantly
different in the different pathological type, and diameter showed
significant independent influence on different pathological type after
binary logistic regression (P < 0.05). Conclusion CA125, HE4,
ROMA, diameter of tumor, D-dimer and age were found significantly
different between stage I and stage II, with age shows good effect on
the diagnosis for stage II and diameter of tumor shows diagnostic value
for non-serous ovarian cancer. Combined diagnosis may improve the
diagnosis rate of early ovarian cancer.
Reducing disease and producing food: Effects of 13 agrochemicals on snail biomass and human schistosomes
Authors: Haggerty Christopher , Halstead Neal , Civitello David , Rohr Jason
Published: March 2022

Agrochemical use is predicted to increase 2-5 fold by 2050 to meet food
demand. Evidence suggests that agrochemical pollution could increase
snails that transmit the disease schistosomiasis to 250 million people,
but most agrochemicals remain unexamined. Here we quantify the relative
effects of fertilizer, six insecticides, and six herbicides on snail
genera responsible for 90% of global schistosomiasis cases. We
identified fertilizers and 4 of 6 insecticides as high risk for
increasing snail biomass by increasing snail habitat (aquatic
vegetation) or food (periphyton) and reducing snail predators,
respectively. Herbicides generally had negative effects on snails by
reducing habitat, with two herbicides increasing snails in the absence
of aquatic vegetation. Parasite production, which reflects human
infection risk, scaled positively to snail biomass. Our findings suggest
that fertilizers and insecticides present higher chances of increasing
human schistosomiasis than herbicides, and revealed several low risk
agrochemicals might help increase crop production without increasing
schistosomiasis.
The impact of block size on treatment imbalance and blinding integrity in randomized clinical trials
Authors: Wang Peijin , Chow Sheinchung
Published: March 2022

Randomization is very important in clinical trials which can prevent
selection bias and valid statistical inference. Block randomization is
often considered to prevent treatment imbalance in comparative clinical
trials, especially when the sample size is small, or subjects’
characteristics change overtime. In practice, however, treatment
imbalance may still occur, especially in multi-center clinical trials.
Breaching blindness in clinical trials is another serious problem
leading to subjective judgement and observational bias. In this article,
we consider two fixed block randomization design with block size of 4
and 2 when comparing a placebo or an active control and a test treatment
under investigation. The probabilities of observing various degrees of
imbalance and the probabilities of correctly guessing the treatment
under three types of prior knowledge are investigated. The results show
that smaller block size design is more likely to maintain treatment
balance than larger block size; however, the difference of imbalance
between the two designs decreases when the sample size gets larger. The
number of subjects per site in multi-center trials also has impact on
the degree of imbalance. Additionally, both block size and prior
knowledge have impact on the probability of guessing the treatment
right. Large sample size in conjunction with varying block size are
suggested for keeping treatment balance and avoiding the chance of
guessers to guess the treatment right.
Effects of subcutaneous injection after coolant spray on pain, hematoma, and ecchymosis in three different regions
Authors: IŞIK MERYEM TÜRKAN , Öztunç Gürsel
Published: March 2022

Aims: This study determined the effect of subcutaneous (SC) low
molecular weight heparin (LMWH) injection in three different areas
(abdomen, leg, and upper arm) after coolant spray application on pain,
hematoma, and ecchymosis formation. Methods: The sample of this
randomized controlled study consisted of 50 patients that were
administered SC LMWH once a day. The SC injection occurred after
applying coolant spray to the arm, leg, or abdominal region. The sample
of this randomized controlled study consisted of 50 patients that were
administered SC LMWH once a day. The SC injection occurred after
applying coolant spray to the arm, leg, or abdominal region. Results:
The study determined that there was no statistically significant
difference in pain severity, hematoma, and ecchymoses between the
regions of SC injection after coolant spray was applied
(p>0.05). However, the highest average pain intensity
directly and 15 minutes after the SC injection was in the leg region.
Conclusion: SC injection after coolant spray application in three
different regions led to the biggest hematoma in the abdominal region,
the biggest ecchymosis in the arm region, and the lowest pain severity
in the abdominal and arm regions. Key words: Coolant spray, ecchymosis,
hematoma, pain, subcutaneous injection (SC).
Psychosocial factors relating to inadequate and excessive weight gain in pregnancy: A narrative, scoping review
Authors: Athar Unsa , Fatima Noor , Waqar Nayab , Shahzad Qanita
Published: March 2022

Many physical factors affecting gestational weight gain have been
studied, the psychosocial aspect of this needs to be looked under the
microscope, especially in low socio-economic countries. A scoping review
of the articles published in the last five years exhibits that perinatal
outcomes like gestational weight are influenced by certain psychosocial
factors, including but not limited to intimate partner violence, lack of
social support and recognition, financial distress, household food
insecurity, chronic stress and depression related to pregnancy, eating
pathologies and low self-esteem. Employing a multi-disciplinary approach
can help us mitigate undesirable outcomes of inadequate and excessive
weight gain.
Risk Factors for Venous Thromboembolism in Pregnancy and Postpartum: A Systematic Review and Meta-analysis
Authors: QIN Chunxiang , Tang Siyuan , CHEN Jiarui , LU Jing , XIE Jiaying , SUN Mei , QIN Chunxiang
Published: March 2022

Background: Venous thromboembolism (VTE) is a disease that could
endanger maternal health, especially its serious complications. Although
several previous studies have examined many risk factors of VTE in
pregnancy and postpartum, we still lack studies that use quantitative
methods to evaluate the strength, quality, and consistency of existing
evidence. Objectives: to summarize risk factors for VTE in pregnancy and
postpartum. Search Strategy: The search was conducted in PubMed、EMBASE,
web of science、MEDLINE. Selection Criteria: Study reporting risk
factors for VTE in pregnancy and postpartum. Data Collection and
Analysis: Review Manager (RevMan, version 5.3) was used for
meta-analysis, and the outcome of the analysis was presented as odds
ratio (OR). Main Results: We included 24 studies (7 case-control
studies, 2 nested case-control studies and 15 cohort studies) and 14 of
them were used for the meta-analysis. There were 59 risk factors with
positive evidence in all studies and we selected 13 risk factors for the
meta-analysis. The three most significant risk factors in the
meta-analysis were Factor V Leiden (FVL) (OR = 9.95, 95% CI:
5.93–16.70), Placenta previa (OR = 8.74, 95% CI: 3.40–22.50), and
cardiac disease (OR = 7.77, 95% CI: 5.31–11.38). Conclusions: The
number of risk factors for VTE during pregnancy and postpartum is very
huge. Our study showed that the main risk factors are advanced age,
overweight, cesarean section, multiple pregnancy, placenta previa, FVL,
F2 20210A and cardiac disease.
The CO2 mitigation and Exergo- and Environ- economics analysis of Bio-gas integrated Semi-transparent Photo-voltaic Thermal (Bi-iSPVT) system for Indian composite climate
Authors: Tiwari G. , Srivastava Praveen , Sinha A , Tiwari A.
Published: March 2022

It is to be noted that bio-gas production is drastically reduced in cold
climatic condition especially in winter due to drop in ambient air
temperature which is much below optimum temperature of about 37 for
fermentation of slurry. Many methods namely hot charging, passive/active
for slurry heating has been tested and it has been found that the
passive heating method is neither practical nor self-sustained. In order
to make bio-gas heating with self-sustained, economical and friendly
with an ecology and environment, new approach of Bi-iSPVT, has been
adopted. Based on the finding, we have made an attempt to analyze the
system in terms of CO2 mitigation, energy matrices and environ- and
exergo-economics to have clean environment and sustainable climate. The
analysis has been done by using embodied energy, annual overall thermal
exergy of the system for ecological balance for good health of human
being. It has been found that an energy payback time (EPBT) for
sustainable Bi-iSPVT system is about 1.67years along with an
exergo-economic parameter (Rex) of 0.1016 kWh/₹.
Modeling epidemics by means of the stochastic description of complex systems
Authors: Carbonaro Bruno
Published: March 2022

The aim of the present paper is to show a way in which the problem of
predicting the evolution of an epidemic may be tackled by describing it
in the framework of Boltzmann’s kinetic theory, as it has been developed
and applied in the last years to complex systems by a suitable
modification of the Boltzmann equation, a suitable re-interpretation of
state variables and the introduction of the notion of «functional
subsystems». Accordingly, in this paper we model an arbitrary (national)
population S as a complex system, split in two functional subsystems,
the first containing all single individuals of S and the second
containing the «care tools», that are to be meant as available places in
hospitals with a sufficient number of physicians and of equipments for
intensive cares. The state variable on the first subsystem will be the
«health state», and the state variable on the other will be the
«effectiveness». We shall then write a system of non-linear ordinary
differential equations which gives the evolution of the probability
distribution on the set of possible values of the health states. By
assigning data partly on the basis of plausibility assumption and partly
as estimated from those furnished by institutions of Campania region,
the system takes a form allowing the numerical simulation of such
evolution, which will be performed and presented in a forthcoming paper.
Pre-screwing Electrocardiographic Characteristics in Guiding Electrode Implantation During Left Bundle Branch Pacing
Authors: Zhuo Shan , Jiang Long , Cai Xiao , Jiang Fei , Zeng Wei , Zhong Jin , Wu Hao , Peng Xin , Shen Jia
Published: March 2022

This study analyzed the characteristics of electrocardiograms recorded
before electrode screwing and at the site of lead fixation during LBBP.
The study aims to establish an electrocardiographic vector-guided method
for electrode implantation during LBBP. Methods: 140 patients who
underwent successful LBBP and had ECGs recorded before electrode
screwing (pre-screwing) and at the site of lead fixation
(post-implantation) were included in the study. Patients whose
post-implantation ECGs revealed rSR’ or M morphologies in lead V1 were
enrolled in the typical right bundle branch (RBBB) group, and those
whose ECGs revealed qR, QR, Qr or QS morphologies in V1 were enrolled in
the atypical RBBB group. Electrocardiographic characteristics of
pre-screwing and post-implantation ECGs were thoroughly analyzed.
Results: For the electrocardiograms of typical RBBB group, pre-screwing
R-wave amplitudes in lead I, aVL, V4, and V5 were 0.6635 (0.433,0.866),
0.69 (0.487,0.866), 0.6635 (0.514,1.489), and 1.056 (0.677,1.840)mv,
respectively; post-implantation QRS transition zone was 1 (0.5,3), and
Stim-LVAT was 68 (61,74)ms. For the atypical RBBB group, pre-screwing
R-wave amplitudes in lead I, aVL, V4 and V5 were 0.527 (0.379,0.704),
0.5285 (0.2985,0.785), 0.5545 (0.2165,1.11), and 0.8525 (0.4737,1.42),
respectively; post-implantation QRS transition zone was 2 (1,3), and
Stim-LVAT was 76 (65,81)ms. The between-group difference were
statistically significant for all the parameters. Conclusion: In
pre-screwing electrocardiograms, R-wave amplitude ≥0.35mV in aVL is a
highly sensitive indicator for predicting typical RBBB morphologies in
left bundle branch pacing, and R-wave amplitude≥0.7mV in lead I is an
indicator with high specificity.
From skirmishes to protracted battles: a bibliometric analysis about human beings and coronaviruses from 1991 to 2020
Authors: Yue Ling , Fu Youjuan , LI Yuanquan , Huang Jiayi , Wang Yifei , Zhu Ziyi , Wang Zhiyang , Li Jing , Chen Wei , He Chao
Published: March 2022

Background: The coronavirus disease 2019 pandemic (COVID-19) has caused
an unprecedented upsurge in the publication of scientific studies as the
global community has collaborated to control the spread of the disease.
Methods: We conducted a bibliometric analysis to evaluate the research
trends and identify the core content based on publication output, the
geographic distribution, collaborations and keywords. We searched for
articles published from 1900 to June 30, 2020 based on the Science
Citation Index Expanded (SCIE) and Social Sciences Citation Index (SSCI)
in the Web of Science. Results: Our analysis revealed the following: (1)
The number of publications clearly increased after the severe acute
respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)
outbreaks and sharply increased during the COVID-19 outbreak. Compared
with SARS and MERS, COVID-19 generated a more dramatic and prolonged
upsurge in publication. (2) Compared with SARS and MERS, COVID-19 had a
more widespread and powerful effect on countries and territories, with a
rapid onset. Countries and territories engaged in more international
collaboration and communication to cope with the epidemics, and the
COVID-19 pandemic led to marked increases in research advancements. (3)
Based on the keywords, we found that multiple methods were used to
address the COVID-19 pandemic that were based on biology, especially the
immune response. Conclusions: Epidemics lead to an extreme acceleration
and changes in research.
Chemical Reactivity and Binding Interactions in RNA−Peptide Complexes
Authors: Srivastava Ruby
Published: March 2022

Abstract: The covalent and noncovalent backbone binding interactions in
RNA-peptide complexes were studied by DFT methods. RNA1 (GGCUAGCC)
structure has been selected for eight protonated peptides (GR, VR, DR,
ER, KR, RR, NGR, tmeGnd) interactions based on an experimental study
(Anal. Chem. 2019, 91, 1659−1664). Several DFT-based global reactivity
descriptors are used to study the reactivity of eight peptides by
chemical reactivity method. High hardness reflects high stability and
low reactivity for the protonated peptides. DR, ER, GR, KR, RR, VR, NGR
show lower value of ω, µ while tmegnd has high value of ω, µ. Larger
HOMO-LUMO gap (7.29 eV) show greater structural stability for peptides.
Autodock results indicated that RNA1 form hairpin structure while
interacting with peptide complexes. (RNA1-RR) has higher binding
energies and RNA1-ER complexes have lower binding energies. Autodock
results showed strong noncovalent interaction as compared to the
covalent RNA backbone bonds interactions, which is also seen by NCIPLOT
and IGMPLOT plots. The reason for it might be due to the proton transfer
from protonated ligand to deprotonated RNA which initiated loss of the
ligand and proton transfer becomes energetically unfavourable in
presence of additional hydrogen bonds as verified by the experimental
results.
Solving the Sample Size Problem for Resource Selection Analysis
Authors: Street Garrett , Potts Jonathan , Börger Luca , Beasley James , Demarais Stevew , Fryxell John , McLoughlin Philip , Monteith Kevin , Prokopenko Christina , Ribeiro Milton , Rodgers Arthur , Strickland Bronson , Beest Floris van , Bernasconi David , Beumer Larissa , Dharmarajan Guha , Dwinnel Samantha , Keiter David , Keuroghlian Alexine , Newediuk Levi , Oshima Júlia , Rhodes Olin , Schlichting Peter , Schmidt Neils , Wal Eric Vander
Published: March 2022

Resource selection analysis (RSA) is a cornerstone approach for
understanding animal distributions, yet there exists no rigorous
quantification of sample sizes required to obtain reliable results. We
provide closed-form mathematical expressions for both the number of
animals and relocations per animal required for parameterising RSA to a
given degree of precision. Required sample sizes depend on just two
quantities: habitat selection strength and an index of landscape
complexity, which we define rigorously. We validate our solutions using
5,678,623 GPS locations from 511 animals from 10 species (omnivores,
carnivores, and herbivores from boreal, temperate, and tropical forests,
montane woodlands, swamps, and tundra). Our results contradict
conventional wisdom by showing that environmental effects on
distributions can often be estimated with fewer animals and relocations
than assumed, with far-reaching implications for ecologists,
conservationists, and natural resource managers.
Effect of irrigation regimes and foliar nutrition on flower development and water productivity of olive (Olea europaea cv. ‘Shengeh’)
Authors: Tadayon Mohammad saeed , Hosseini Seyed Mashaallah , Sadeghi Sohrab
Published: March 2022

Background: Despite the high productivity in temperate regions, the
olive has a poor yield, under environmental stress due to the
inappropriate flower bud development and increment of staminate flowers.
Objectives: In this experiment, the effect of irrigation regimes and
foliar nutrition with nitrogen, calcium, zinc and boron on this
complication was investigated. Methods: Two experimental factors
contained irrigation regimes - irrigation to 50 percent of maximum
allowable depletion (MAD) (Control) (I50) – increasing the irrigation
to 25 percent of MAD during flower initiation (I25init) - increasing the
irrigation to 25 percent of MAD during olive flower induction (I25ind),
and I25init + I25ind; and foliar nutrition - without treatment
(control), and foliar nutrition with 2% urea fertilizer; 2% Ca-EDTA
chelate, 9.5% Ca; 0.2 % Zn-EDTA chelate and 0.2 % boric acid, during
flower initiation (FNinit), flower induction (FNind) and FNinit + FNind.
Results: The results indicated that the increment of irrigation water to
25 percent of MAD during flower initiation along with foliar nutrition
at both times had the highest influence on the increment of perfect
ﬂowers with 3-4 developed ovules. This treatment had the highest water
productivity and fruit oil content and can be recommended for olive
groves under drought stress.