Deep inverse reinforcement learning for structural evolution of small molecules.

The size and quality of chemical libraries to the drug discovery pipeline are crucial for developing new drugs or repurposing existing drugs. Existing techniques such as combinatorial organic synthesis and high-throughput screening usually make the process extraordinarily tough and complicated since the search space of synthetically feasible drugs is exorbitantly huge. While reinforcement learning has been mostly exploited in the literature for generating novel compounds, the requirement of designing a reward function that succinctly represents the learning objective could prove daunting in certain complex domains. Generative adversarial network-based methods also mostly discard the discriminator after training and could be hard to train. In this study, we propose a framework for training a compound generator and learn a transferable reward function based on the entropy maximization inverse reinforcement learning (IRL) paradigm. We show from our experiments that the IRL route offers a rational alternative for generating chemical compounds in domains where reward function engineering may be less appealing or impossible while data exhibiting the desired objective is readily available.

Multi-view self-attention for interpretable drug-target interaction prediction.

The drug discovery stage is a vital aspect of the drug development process and forms part of the initial stages of the development pipeline. In recent times, machine learning-based methods are actively being used to model drug-target interactions for rational drug discovery due to the successful application of these methods in other domains. In machine learning approaches, the numerical representation of molecules is critical to the performance of the model. While significant progress has been made in molecular representation engineering, this has resulted in several descriptors for both targets and compounds. Also, the interpretability of model predictions is a vital feature that could have several pharmacological applications. In this study, we propose a self-attention-based multi-view representation learning approach for modeling drug-target interactions. We evaluated our approach using three benchmark kinase datasets and compared the proposed method to some baseline models. Our experimental results demonstrate the ability of our method to achieve competitive prediction performance and offer biologically plausible drug-target interaction interpretations.

Characterization of a highly stable α-galactosidase from thermophilic Rasamsonia emersonii heterologously expressed in a modified Pichia pastoris expression system.

BACKGROUND: Structurally stable α-galactosidases are of great interest for various biotechnological applications. More thermophilic α-galactosidases with high activity and structural stability have therefore to be mined and characterized. On the other hand, few studies have been performed to prominently enhance the AOX1 promoter activity in the commonly used Pichia pastoris system, in which production of some heterologous proteins are insufficient for further study. RESULTS: ReGal2 encoding a thermoactive α-galactosidase was identified from the thermophilic (hemi)cellulolytic fungus Rasamsonia emersonii. Significantly increased production of ReGal2 was achieved when ReGal2 was expressed in an engineered Pastoris pichia expression system with a modified AOX1 promoter and simultaneous fortified expression of Mxr1 that is involved in transcriptionally activating AOX1. Purified ReGal2 exists as an oligomer and has remarkable thermo-activity and thermo-tolerance, exhibiting maximum activity of 935 U/mg towards pNPGal at 80 °C and retaining full activity after incubation at 70 °C for 60 h. ReGal2 is insensitive to treatments by many metal ions and exhibits superior tolerance to protein denaturants. Moreover, ReGal2 efficiently hydrolyzed stachyose and raffinose in soybeans at 70 °C in 3 h and 24 h, respectively. CONCLUSION: A modified P. pichia expression system with significantly enhanced AOX1 promoter activity has been established, in which ReGal2 production is markedly elevated to facilitate downstream purification and characterization. Purified ReGal2 exhibited prominent features in thermostability, catalytic activity, and resistance to protein denaturants. ReGal2 thus holds great potential in relevant biotechnological applications.

Epidemiological survey of sheep as potential hosts for Leishmania in China.

BACKGROUND: Leishmania parasites cause visceral leishmaniasis (VL), an important infectious disease that is endemic to large parts of the world and often leads to epidemics. Sand flies are the primary transmission vector for the parasite in endemic regions. We hypothesized that sheep might serve as an overlooked reservoir for Leishmania transmission to humans due to the asymptomatic nature of infection in many species. As a preliminary test of this hypothesis, the aim of the present study was to investigate sheep in an area of China that is endemic for the desert sub-type of zoonotic VL and establish if they are potential carriers of Leishmania. RESULTS: Sheep tissue samples were collected from abattoirs in VL endemic areas of Jiashi County, China during the non-transmission season. rK39 immunochromatographic tests were performed to detect the presence of the parasite in blood samples. In addition, DNA was extracted from the blood, and used for detection of the Leishmania-specific internal transcribed spacer-1 (ITS-1) genomic region using a nested polymerase chain reaction (PCR) approach. PCR products were further analyzed to identify restriction fragment-length polymorphism patterns and representative sequences of each pattern were selected for phylogenetic analysis. The rK-39 and nested PCR data indicated positive detection rates for Leishmania in sheep of 26.32 and 54.39%, respectively. The phylogenetic analysis revealed that all of the samples belonged to the species L. infantum and were closely related to strains isolated from human infections in the same area. CONCLUSIONS: Sheep could be a potential host for Leishmania in VL endemic areas in China and may be an overlooked reservoir of human VL transmission in this region. To further confirm livestock as a potential host, further verification is required using a sand fly biting experiment.

[Research Advances on Distribution Characteristics of and Factors Associated with Fecal Contamination by Definitive Hosts of Echinococcus spp.].

Echinococcosis is a severe zoonotic parasitic disease caused by larvae of Echinococcus spp.. Fecal contamination by definitive hosts of Echinococcus is the major cause of echinococcosis transmission. It is therefore of great significance to estimate the level of fecal contamination by the definitive hosts and develop prevention and control strategies. This article gives an overview on distribution characteristics of, and factors associated with fecal contamination by definitive hosts of Echinococcus.

[Cost Analysis of Dog Deworming in Echinococcosis Control Program in Daofu，Sichuan Province].

Objective: To estimate the cost of dog deworming in Daofu, Sichuan Province and analyze the factors influencing the cost, in order to provide a scientific basis for the investment for echinococcosis control. Methods: Thirty villages were randomly selected in Daofu, Sichuan Province in November 2015, according to the proportion of agricultural and pastoral areas. Data concerning the cost during each step of dog deworming were collected. The unit cost was estimated, the cost composition in each step, element, and institution were described, and the main cost-influencing factors were analyzed using the linear regression method. Results: The mean cost of dog deworming in the 30 surveyed villages was 3.76 yuan/dog-times, comprising drug cost of 0.38 yuan/dog-times, bait cost of 0.37 yuan/dog-times, drug delivery cost of 0.09 yuan/dog-times, mobilization cost of 0.19 yuan/dog-times, household deworming cost of 2.05 yuan/dog-times, faeces disposal cost of 0.35 yuan/dog-times, training cost of 0.29 yuan/dog-times, and supervision cost of 0.04 yuan/dog-times. Among the deworming steps, household deworming cost occupied the most （2.05 yuan/dog-times）; among the cost elements, labour cost had the highest proportion （2.55 yuan/dog-times）; among the different-leveled institutions, village-level cost was the most important part（2.82 yuan/dog-times）. Linear regression analysis revealed that the type of production and the distance among households were the major influencing factors. The labour price was the most sensitive factor for cost-estimation in the dog deworming activities. Conclusion: The labor cost of dog deworming is very high. Governments should increase investment according to local situations.

[Dog Fecal Contamination by Echinococcus in Cuomei County of Tibet in 2015].

Objective: To understand dog fecal contamination by Echinococcus in Lhoka Prefecture of Tibet and provide basis for development of prevention and control strategies. Methods: Survey spots were sampled around the Zhegu Village of Zhegu Town in Cuomei County of Tibet using the mechanical sampling method in May, 2015. The positions of spots, amount of dog feces, types of camps, pastures, terrains, vegetations and land cover, as well as information concerning the existence of household garbage, were recorded. The linear distance from survey spot to the center of the village was calculated. Dog feces were sampled in survey spot and examined the copro-antigen for Echinococcus contamination by ELISA. The distribution characteristics of fecal contamination were analyzed by chi-square test, Fisher's exact test, Kruskal-Wallis test and Nemenyi test. Results: Seventy-nine survey spots were selected for sampling. A total of 226 feces samples were obtained in 37 of the spots. ELISA results showed that the copro-antigen positive rate was 23.9%（54/226）, the averaged density of feces and the averaged density of positive feces were 0.317 9/100 m2 and 0.075 9/100 m2, with a maximum of 2.555 6/100 m2 and 0.555 6/100 m2 respectively. The density of feces and the density of positive feces were both higher in summer camps（0.601 9/100 m2 and 0.157 4/100 m2 respectively） than in non-camps（0.170 2/100 m2 and 0.033 1/100 m2）（χ2=18.248 4，P<0.01；χ2=15.274 3，P<0.01）. In addition, the density of feces and the density of positive feces were both higher in survey spots with household garbage（0.679 0/100 m2, 0.177 0/100 m2） than in those without household garbage （0.130 3/100 m2 and 0.023 5/100 m2）（χ2=34.634 7，P<0.01；χ2=26.109 1，P<0.01）; as well as higher in survey spots ≥10 km from the center of the village（0.403 7/100 m2, 0.107 4/100 m2） than in those <10 km（0.265 3/100 m2, 0.056 7/100 m2）（χ2=4.432 7，P<0.05；χ2=4.045 5，P<0.05）. Conclusion: The Cuomei County of Tibet is facing a serious situation of dog fecal contamination by Echinococcus. Summer camps, areas with household garbage, and districts with a ≥10 km linear distance from the village center may provide reference for determining the regions for hydatidosis prevention and control.

Two nanocage-based metal-organic frameworks with mixed-cluster SBUs and CO2 sorption selectivity.

Two nanocage-based metal-organic frameworks respectively built on two and three types of clusters with diisophthalate ligand were constructed, displaying unprecedented (3,4,6)-connected nets, unusual nanocages, and new bipaddle-wheel tetranuclear cluster, as well as highly selective CO2 capture.

Analysis on Serum Trace Element Levels of Echinococciasis Patients in Garze Tibetan Autonomous Prefecture in Sichuan, China, 2011.

In Garze Tibetan autonomous prefecture in Sichuan province, China, 41 echinococciasis patients who had received surgical treatment were recruited in the study, and 82 health persons who had lived in Garze for at least 10 years were selected as controls. The serum levels of Zn, Se and Cu of the cases and controls were detected. The results showed that most echinococciasis cases were distributed in Shiqu county (17.1%, 7/41), and only 1 case was distributed in Yajiang county (2.4%). The male to female ratio of the cases was 1:1.56. The echinococciasis patients were mainly aged 30-39 years (36.59%, 15/41). And, the cases aged 20-49 years accounted for 68.29% (28/41). Compared with health controls, the serum levels of Zn and Se of the cases significantly declined. However, the serum level of Cu of the cases had no significantly change. It was confirmed that the serum levels of Zn and Se were interrelated with the prevalence of echinococciasis.

[Progress on the epidemiology of echinococcosis].

Echinococcosis is a zoonotic parasitic disease caused by the larval stages belonging to the genus Echinococcus. Echinococcosis is a major public health problem in many countries and regions. The epidemiological study of echinococcosis would contribute to the control and elimination of this disease. This paper summarizes the research status and progress on epidemiology of echinococcosis.

[Analysis of larval echinococcosis cases from the National Web-based Infectious Diseases Report System in China in 2011].

OBJECTIVE: To analyze the relevant information of echinococcosis cases from the National Web-based Infectious Diseases Report System in China in 2011. METHODS: Data of echinococcosis in 2011 were collected from the Report System of the Chinese Center for Disease Control and Prevention. SPSS 16.0 software was used to analyze the data. RESULTS: A total of 3 225 cases were reported in 2011, including 1 death and 3 013 effective cases. The three provinces (autonomous region) with high incidence were Xinjiang (occupying 41.5%, 1251/3013), Gansu (16.9%, 509/3 013) and Qinghai (12.0%, 363/3 013). Cases distributed in all age groups, with the highest incidence in the group of 31-40-year-old. Male to female ratio was 1:1.01. The incidence of farmers and herdsmen was highest. CONCLUSION: In 2011, the reported cases are mainly distributed in Xinjiang, Qinghai, Inner Mongolia, Gansu, Ningxia, Sichuan and Tibet. Echinococcosis is mainly prevalent in western China.

Three new species of Nazeris Fauvel from the Jiuwan Mountain, Guangxi, China (Coleoptera, Staphylinidae, Paederinae).

Three new species of Nazeris Fauvel, 1873 from the Jiuwan Mountain, Guangxi, China, are described and illustrated: N. jiuwanensis, sp. n., N. qingshuius, sp. n. and N. yangmeius sp. n. An identification key to the Nazeris species in Guangxi is provided.

[Prognostic value of aquaporin-4 antibody in patients of inflammatory demyelinating diseases in central nervous system].

OBJECTIVE: To determine the prognostic value of AQP4 antibody in the cohort of Chinese patients with neuromyelitis optical (NMO), HR-NMO (high-risk NMO)and classic multiple sclerosis (MS). METHODS: Sera of patients with NMO, HR-NMO and MS were all investigated for the presence of AQP4 antibody by indirect immunofluorescence in human AQP4-transfected cells. The diagnostic and prognostic values of anti-AQP4 antibody were evaluated in 352 patients with NMO (n=106), HR-NMO (n=84) including optico-spinal MS (OSMS), longitudinally extensive transverse myelitis (LETM), recurrent optic neuritis (RON) and optic neuritis (ON) or transverse myelitis (TM) with other autoimmune disease and classic MS (n=162). All patients were followed up at outpatient clinics or by telephone. RESULTS: In our study, the anti-AQP4 antibody's seropositivity in all demyelinating cases (n=352) was 31.3%. And 72 (65.5%) seropositive patients presented with severe ON, 82 (74.5%) with TM, 60 (54.4%) with spinal-cord lesion more than 3 segments, 16 (14.5%) had relapses of ON and 38 (34.5%) relapses of TM during a follow-up period of 24 months. Significant differences existed between anti-AQP4 antibody seropositivity and seronegative in terms of concurrent severe ON, TM, spinal-cord lesion more than 3 segments and relapses of ON and TM (P<0.05). Also, in NMO patient seropositive for anti-AQP4 antibody (n=78), 28 (35.9%) developed relapses of TM. However, in HR-NMO patient with seropositivity (n=28), 4 (14.3%) developed relapses of ON and 10 (35.7%) relapses of TM. The relapse of ON or TM occurred in 57/110 seropositive patients versus 17/242 seronegative ones (P<0.05). CONCLUSION: As compared with anti-AQP4 antibody-negative ones, anti-AQP4 antibody-positive patients show significantly higher frequencies of severe ON, TM, longitudinal spinal-cord segments and they are more predisposed to ON or TM relapse. And seropositive NMO and HR-NMO patients are more likely to develop relapses of ON or TM. Anti-AQP4 antibody may play some roles in the diagnosis and prognostic predication of demyelinating diseases in central nervous system.

[Neuropsychological features of elderly patients with mild cognitive impairment susceptible to Alzheimer's disease].

OBJECTIVE: To explore the neuropsychological features of elderly patients with mild cognitive impairment (MCI) susceptible to Alzheimer's disease (AD). METHODS: A total of 47 patients with MCI diagnosed from June to October 2008 and 21 controls with normal cognition at the same convalescent camp were selected and followed up for two years. Montreal cognitive assessment (MoCA), mini mental state examination (MMSE) and clock drawing test (CDT) were performed for all subjects at the onset of study and repeated annually. RESULTS: At Month 12, the visuospatial skill scores of MCI patients decreased significantly versus those of the control (0.6 ± 0.7 vs 0.1 ± 0.6, P = 0.008). No one progressed to AD in neither groups. And at Month 24, both visuospatial skill scores (0.9 ± 0.9 vs 0.4 ± 0.9) and attention scores (1.0 ± 1.0 vs 0.2 ± 0.8) of MCI patients declined significantly versus the control (P = 0.021, 0.001). Among 47 MCI patients, 7 progressed to AD. No obvious difference existed in the score of all items between the AD converters and non-converters at baseline. However, the scores of MMSE (27.6 ± 0.8 vs 28.9 ± 1.0), MoCA (24.3 ± 3.1 vs 27.9 ± 1.6) and such MoCA subitems as visuospatial skill (3.9 ± 0.7 vs 4.5 ± 0.6), language (1.86 ± 0.38 vs 2.65 ± 0.53) and delayed recall (2.1 ± 1.5 vs 3.9 ± 1.0) of the converters were obviously lower than those of the non-converters at Month 12 (P < 0.05). Furthermore, all other scores of the AD converters, except for designation and abstract, were significantly lower than those of the non-converters at Month 24 (P < 0.05). CONCLUSION: The visuospatial skill, executive function, delayed recall and language function of MCI patients progressing to AD tend to have early impairment and significant changes. It may be useful to predict AD among the MCI patients.

[Survey on a new case of visceral leishmaniasis in Shanxi Province].

A new case of visceral leishmaniasis (kala-azar) was reported by Changzhi CDC of Shanxi Province in September 2011. The case was investigated clinically and epidemiologically. The patient was a two-year-old boy who lived in Huangnian Town of Changzhi County in Shanxi Province. Clinical examination showed hepatosplenomegaly, consistent decrease of blood cells and Leishman-Donovan body in the bone marrow smear. The rK39 immune diagnosis test showed strongly positive. The case was diagnosed as kala-azar. After one course treatment of sodium stibogluconate, the patient's condition improved markedly. There were no cases of kala-azar in this region historically. Blood samples of 17 individuals and 5 domestic animals including 3 dogs were all negative in the rK39 immunodiagnostic test. It is speculated that the potential risk of kala-azar transmission exists in this region.

[Geographical distribution of echinococcosis among children in Qinghai Province].

OBJECTIVE: To analyze the epidemiological status of echinococcosis among children in three different zones of Qinghai Province. METHODS: B-ultrasound and ELISA were used in the survey to evaluate echinococcus infection among 6 to 15 year old children in the three zones, namely, Qinghai southern plateau, Qilian mountain-Hehuang valley and Chaidamu basin. RESULTS: The prevalence of echinococcus infection scanned by B-ultrasound and sera positive rate detected by ELISA in children were 1.5% (320/20 730) and 6.5% (1024/15 762) respectively, and the prevalence of cystic echinococcosis and alveolar echinococcosis by ultrasound were 1.0% (206/20730) and 0.6% (114/20730), respectively. The prevalence and sera positive rate were 9.5% (707/7 453) and 2.3% (269/11 618) in Qinghai southern plateau, 3.8%(289/7 544) and 0.6% (50/8 275) in Qilian mountain-Hehuang valley, and 3.7% (28/765) and 0.1% (1/837) in Chaidamu basin, respectively. The southern plateau showed the highest prevalence, with a significant statistical difference among the three areas (P < 0.01). The prevalence of alveolar echinococcosis was 1.0% (114/11 618) in the southern plateau, but no alveolar echinococcosis patients were found in other two areas. Correlation analysis showed that the prevalence increased with the altitude (r(s-e) = 0.96, P < 0.05, R2 = 0.93; r(p-e) = 0.82, P < 0.05, R2 = 0.67). CONCLUSION: The prevalence of echinococcosis among children shows an apparent geographical difference in Qinghai Province.

[Assessment of health education against echinococcosis in Tibetan region of Sichuan Province, China].

OBJECTIVE: To find an effective strategy of implementing health education in Tibetan Regions so as to make echinococcosis control sustainable at a large scale. METHODS: During July to November of 2008, surveys were conducted on health education requirements among various populations in the form of questionnaire and group discussion in endemic areas of echinococcosis in three counties of the Ganzi Tibetan Autonomous Prefecture, Sichuan. Based on the obtained results, health education materials suitable for different populations were designed. The materials were applied for conducting health education in field at Tagong Township, Kangding of Ganzi in October, 2009. By the survey in May, 2010, the improved effect on knowledge and behavior change was compared before and after (6 months later) health education in order to assess the usefulness of these materials. Simultaneously, Xinduqiao Township of Kangding was selected as control. This town is neighboring to the study area with similar natural and demographic conditions, in which no health education activities related to the study was implemented. RESULTS: Various populations showed their interested requirements for health education materials and ways. Based on the information collected, a series of materials were designed and applied for health education activities in field. The results indicated that, compared with the data before health education, improvement of the knowledge and behaviors against echinococcosis among students and local residents showed significant increase (P < 0.05), but only one knowledge point about the importance of washing hands before meal among students showed no significant difference (P > 0.05) in spite of the rates increasing from 88.6% (78/88) before health education to 95.5% (84/88) after education. The local officers and monks also showed to some extent improvement on behavior manners. The rate of correct treatment of livestock viscera increased from 37.1% (13/35) and 30.3% (10/33) before the education to 82.9% (29/35) and 78.8% (26/33) (P < 0.01), while the rate of not feeding stray dogs among monks was 6.4% (3/47) before and 10.6% (5/47) (P > 0.05) after the education. The knowledge-increasing and behavior-improving rates on playing dogs among the students, residents and monks increased by 182% and 193%, 42.8% and 54.3%, 6.4% and 14.9%, respectively. There was no considerable change in the control township. CONCLUSION: The materials designed for health education are acceptable by most populations. The improvement rate of knowledge and behaviors is considerable among the groups. Use of the materials receives expected effect on health education and health promotion.

Societal drivers of human echinococcosis in China.

BACKGROUND: Echinococcosis is a parasitic zoonotic disease that threatens human health and economic development. In China, 370 counties are endemic for echinococcosis. Qinghai-Tibet Plateau has the most patients and people at risk. Therefore, analyzing the societal factors related to susceptibility to the disease is critical for efficient prevention and control of echinococcosis. METHODS: The demographic characteristics and lifestyle of echinococcosis cases were clustered using K-means cluster analysis to determine the main factors of risk of echinococcosis. RESULTS: Middle-aged and young people as well as those with a low education level and herdsmen are at risk of contracting echinococcosis. Nomadism, domestic and feral dogs in the surrounding environment, and drinking heavily polluted natural surface water are the main behavioral risk factors. The cystic echinococcosis (CE) and alveolar echinococcosis (AE) cluster analysis focused on female, middle-aged, and young people, winter settlement and summer nomadism, and domestic and feral dogs in the surrounding environment. There were significant differences in lifestyle between Qinghai-Tibet Plateau cases and non-Qinghai-Tibet-Plateau cases. CONCLUSION: According to the distribution of cases and CE and AE, this study identified the factors of risk of echinococcosis in the Qinghai-Tibet Plateau and non-Qinghai-Tibet Plateau. Adapted control techniques appropriate for the various epidemic areas should be established to serve as a reference for echinococcosis prevention.

Fibrinogen depleting agent batroxobin has a beneficial effect on experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) was characterized with widespread demyelination and axonal loss of central nervous system (CNS). Fibrinogen (fibrin) deposition was considered as one of the pathogenesis of MS. Therefore, we explored the effects of fibrinogen depleting agent batroxobin in experimental autoimmune encephalomyelitis (EAE) mice model. Our study showed that prevention and suppression with batroxobin significantly ameliorated clinical severity of EAE, reduced inflammatory cells infiltration, and demyelination, and suppressed the activation of astrocytes and macrophages comprising the CD11b(+) population. Batroxobin treatment leads to reduced expression of p-Akt and increased expression of MBP as compared to control. In addition, batroxobin treatment partly reversed the dendric-like formation of macrophages irritated by fibrinogen in vitro. The reduced severity of EAE mice treated with batroxobin suggests that strategy targeting fibrin as a potential therapy for EAE may be beneficial for the treatment of MS patients.

Outcomes, and factors affecting outcomes, following shoulder hemiarthroplasty for proximal humeral fracture repair.

BACKGROUND: Hemiarthroplasty has been applied to treat proximal humeral fracture with variable outcomes. The purpose of this retrospective study was to assess factors affecting outcome in patients following hemiarthroplasty for proximal humeral fracture (PHF) repair. METHODS: Patients with proximal humeral fractures treated over a 6-year period were included. Indications for hemiarthroplasty were severe three-part fractures associated with osteoporosis; four-part fractures with or without dislocation; splitting of the humeral head, or >45% collapse of the humeral head. Surgery outcome and postoperative complications were main outcome measures in this study. RESULTS: Thirty-three of 47 patients were included in the final analysis (mean age 64.3 years, range 43-82). Mean postoperative follow-up was 44.4 (range 36-57) months. Postoperative complications (shoulder dislocation, mild shoulder subluxation, heterotopic ossification) occurred in seven patients. Healing of the greater and lesser tubercles was abnormal or poor in 18 patients. These patients had significantly higher pain scores (4.0 ± 1.1 vs. 2.2 ± 1.1) and significantly lower capacities for active lifting (79.3 ± 9.6 vs. 121.7 ± 24.3), external rotation (20.7 ± 3.7 vs. 39.2 ± 10.3), and Neer scores (79.2 ± 5.7 vs. 90.6 ± 3.6) versus patients who exhibited complete healing (all P < 0.001). Patient age, type of surgical approach, and fracture type were not major influencers of outcome. CONCLUSION: In conclusion, the healing of the greater and lesser tubercles is the major determinant of outcome following hemiarthroplasty for PHF repair.